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1.
J Am Chem Soc ; 142(9): 4254-4264, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045520

RESUMO

By taking advantage of well-defined spectroscopic signatures of high-quality CdSe/CdS core/shell QDs, the effects of oxygen on photoluminescence (PL) of QDs were studied systematically and quantitatively at both single-dot and ensemble (on substrate and in solution) levels, which reveals a unified yet simple picture. With a sufficient amount of oxygen in the system during photoexcitation, the core/shell QDs in all forms would be deionized timely from the photogenerated and inefficient trion state back to the efficient single-exciton state, with superoxide radicals as the reduction product of oxygen. Under a given excitation power, rates of both spontaneous deionization and photodeionization channels increased by increasing the oxygen pressure, but photoionization of the QDs was barely affected by the oxygen pressure. While stabilizing PL by oxygen was identified for both CdSe plain core and CdSe/CdS core/shell QDs, irreversible photocorrosion was only observed for CdSe plain core QDs, suggesting the importance of high-quality epitaxial shells for QDs in various applications.

2.
J Cell Mol Med ; 24(5): 3022-3033, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989756

RESUMO

Chicoric acid is polyphenol of natural plant and has a variety of bioactivity. Caused by various kinds of stimulating factors, acute liver injury has high fatality rate. The effect of chicoric acid in acute liver injury induced by Lipopolysaccharide (LPS) and d-galactosamine (d-GalN) was investigated in this study. The results showed that CA decreased the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and reduced the mortality induced by LPS/d-GalN. CA can restrain mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) to alleviate inflammation. Meanwhile, the results indicated CA can active nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway with increasing the level of AMP-activated protein kinase (AMPK). And with the treatment of CA, protein levels of autophagy genes were obvious improved. The results of experiments indicate that CA has protective effect in liver injury, and the activation of AMPK and autophagy may make sense.

3.
Int J Cancer ; 146(8): 2243-2254, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525277

RESUMO

Constitutive activation of FGFR1, as a result of diverse chromosome translocations, is the hallmark of stem cell leukemia/lymphoma syndrome. The BCR-FGFR1 variant is unique in that the BCR component contributes a serine-threonine kinase (STK) to the N-terminal end of the chimeric FGFR1 kinase. We have deleted the STK domain and mutated the critical Y177 residue and demonstrate that the transforming activity of these mutated genes is reduced compared to the BCR-FGFR1 parental kinase. In addition, we demonstrate that deletion of the FGFR1 tyrosine kinase domain abrogates transforming ability, which is not compensated for by BCR STK activity. Unbiased screening for proteins that are inactivated as a result of loss of the BCR STK identified activated S6 kinase and SHP2 kinase. Genetic and pharmacological inhibition of SHP2 function in SCLL cells expressing BCR-FGFR1 in vitro leads to reduced viability and increased apoptosis. In vivo treatment of SCLL in mice with SHP099 leads to suppression of leukemogenesis, supporting an important role for SHP2 in FGFR1-driven leukemogenesis. In combination with the BGJ398 FGFR1 inhibitor, cell viability in vitro is further suppressed and acts synergistically with SHP099 in vivo suggesting a potential combined targeted therapy option in this subtype of SCLL disease.

4.
J Chem Phys ; 151(23): 234703, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864257

RESUMO

Auger nonradiative recombination dominates decay of multicarrier states in high quality colloidal quantum dots (QDs) and thus is critical for many of their optical and optoelectronic applications. Controlling interface-potential smoothness and wavefunction delocalization are proposed as two main strategies for Auger engineering in core/shell QDs. Here, a series of CdSe-based core/shell QDs with nearly ideal optical quality of their single-exciton states are developed and applied for studying biexciton quantum yields and Auger nonradiative recombination rates. Comparative experiments find that the interface-potential smoothness has little influence on biexciton quantum yield and Auger rates of these core/shell QDs with the same CdS outer shells. In contrast, with a fixed total size of the series of QDs, the decreasing hole wavefunction delocalization can increase the Auger rates of positive trions by ∼400%. A mild decrease in electron wavefunction delocalization among the series of QDs results in a small increase in the Auger rates of negative trions (∼50%). Smoothing the core/shell interface can indeed affect the Auger rates, but this is by the way of altering wavefunction delocalization. These findings highlight the importance of control of wavefunction delocalization among the strategies of Auger engineering and provide guidelines for rational design QDs for applications.

5.
BMC Anesthesiol ; 19(1): 205, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699052

RESUMO

BACKGROUND: Surgical stress induces the release of neuroendocrine mediators and cytokines during perioperative period, which may have adverse effects on cancer patients. While the surgical stress responsse can be affected by anesthetic technique. Therefore, we designed this study to assess whether subcostal transversus abdominis plane (TAP) block can affect perioperative neuroendocrine stress response, postoperative analgesia and postoperative recovery in patients undergoing radical gastrectomy under general anesthesia. METHODS: Sixty-five patients were recruited. Patients randomly received general anesthesia (control group), or general anesthesia combined with TAP block (40 mL of 0.375% ropivacaine) (TAP group). The primary outcome was neuroendocrine levels including norepinephrine (NE), epinephrine (E), cortisol (Cor), glucose (Glu), interleukin (IL)-6 and IL-10 during 48 h after surgery. Secondary outcomes included pain score, hemodynamic variables and recovery characteristics. RESULTS: Data from 61 of 65 patients were analyzed. The levels of NE, E, Cor, and Glu were blunt by TAP block during perioperative period. The levels of IL-6 and IL-10 were significantly lower in TAP group than in control group. TAP block efficiently relieved postoperative acute pain up to 12 h postoperatively with more stable perioperative hemodynamics compared with control group. CONCLUSIONS: Subcostal TAP block blunts perioperative stress response and provides efficient analgesia, with good hemodynamic stability and minimal adverse effects.

6.
J Am Chem Soc ; 141(44): 17617-17628, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31610655

RESUMO

Wurtzite CdSe@CdS dot@platelet nanocrystals, dot-shaped CdSe nanocrystals encased within epitaxially grown CdS nanoplatelets, are controllably synthesized with nearly monodisperse size and shape distribution and outstanding photoluminescence (PL) properties. The excellent size and shape control with their lateral to thickness dimension ratio up to 3:1 is achieved by systematically studying the synthetic parameters, which results in a simple, tunable, yet reproducible epitaxy scheme. These special types of core/shell nanocrystals possess two-dimensional emission dipoles with the ab plane of the wurtzite structure. While their near-unity PL quantum yield and monoexponential PL decay dynamics are at the same level of the state-of-art CdSe/CdS core/shell nanocrystals in dot shape, CdSe@CdS dot@platelet nanocrystals possess ∼2 orders of magnitude lower probability for initiating PL blinking at the single-nanocrystal level than the dot-shaped counterparts do.

7.
Am J Pathol ; 189(12): 2450-2458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31542393

RESUMO

The WASF3 gene has been implicated in cancer cell movement, invasion, and metastasis by regulating genetic pathways important in these processes. Invasion and metastasis assays, however, are largely centered on xenograft models in immune-compromised mice. To facilitate analysis of the role of WASF3 in the spontaneous development of cancer cell metastasis, we generated a Wasf3 null strain by deleting exons 4 and 5, which encode essential motifs for Wasf3 function. On exposure to cre-recombinase a stop codon is generated immediately downstream in exon 6. Using a cytomegalovirus (CMV)-cre strain, Wasf3 constitutively was inactivated, which led to viable mice with no visible morphologic or behavioral abnormalities. There was no abnormal development or function of the mouse mammary gland in the Wasf3 null mice and brain development was normal. In the mouse mammary tumor virus (MMTV)-driven polyoma middle-T oncogene strain, which shows early onset breast cancer development and metastasis, Wiskott-Aldrich syndrome protein family member 3 (Wasf3) is up-regulated in metastatic lesions. When this oncogene was introduced onto the Wasf3-null background, although metastasis was observed in these mice, there was a reduction in the number and size of metastatic lesions in the lungs. These data provide evidence for a role in WASF3 in the development of metastasis in a spontaneous model of breast cancer.

8.
Adv Sci (Weinh) ; 6(18): 1900412, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31559125

RESUMO

The further practical applications of halide perovskite quantum dots (QDs) are blocked by problems of instability and nonradiative Auger recombination manifested as photoluminescence blinking. Here, single core/shell structured perovskite semiconductor QDs are successfully fabricated by capping CsPbBr3 QD core with CdS shell. It is demonstrated that CsPbBr3/CdS core/shell QDs exhibit ultrahigh chemical stability and nonblinking photoluminescence with high quantum yield due to the reduced electronic traps within the core/shell structure. Efficiency of amplified spontaneous emission exhibits obvious enhancement compared to that of pure CsPbBr3 QDs, originating from the mitigated competition between stimulated emission and suppressed nonradiative biexciton Auger recombination. Furthermore, low-threshold whispering-gallery-mode lasing with a high-quality factor is achieved by incorporating CsPbBr3/CdS QDs into microtubule resonators. Density functional theory (DFT)-based first-principles calculations are also performed to reveal the atomic interface structure, which supports the existence of CsPbBr3/CdS structure. An interesting feature of spatially separated charge density at CsPbBr3/CdS interface is found, which may greatly contribute to the suppressed Auger recombination. The results provide a practical approach to improve the stability and suppress the blinking of halide perovskite QDs, which may pave the way for future applications for various optoelectronic devices.

9.
Front Cell Dev Biol ; 7: 166, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475148

RESUMO

Ceramide-rich platforms (CRPs) mediate association of proteins with the sphingolipid ceramide and may regulate protein interaction in membrane contact sites to the cytoskeleton, organelles, and infectious pathogens. However, visualization of ceramide association to proteins is one of the greatest challenges in understanding the cell biology of ceramide. Here we introduce a novel labeling technique for ceramide-associated proteins (CAPs) by combining photoactivated cross-linking of a bioorthogonal and bifunctional ceramide analog, pacFACer with proximity ligation assays (PLAs). pacFACer cross-linked to CAPs is covalently attached to a fluorophore using click chemistry. PLAs use antibodies to: (1) the candidate CAP and the fluorophore (PLA1); and (2) the CAP and ceramide (PLA2). PLA1 shows the subcellular localization of a particular CAP that is cross-linked to pacFACer, while PLA2 tests if the cross-linked CAP forms a complex with endogenous ceramide. Two proteins, tubulin and voltage-dependent anion channel 1 (VDAC1), were cross-linked to pacFACer and showed PLA signals for a complex with ceramide and pacFACer, which were predominantly colocalized with microtubules and mitochondria, respectively. Binding of tubulin and VDAC1 to ceramide was confirmed by coimmunoprecipitation assays using anti ceramide antibody. Cross-linking to pacFACer was confirmed using click chemistry-mediated attachment of biotin and streptavidin pull-down assays. Inhibition of ceramide synthases with fumonisin B1 (FB1) reduced the degree of pacFACer cross-linking and complex formation with ceramide, while it was enhanced by amyloid beta peptide (Aß). Our results show that endogenous ceramide is critical for mediating cross-linking of CAPs to pacFACer and that a combination of cross-linking with PLAs (cross-link/PLA) is a novel tool to visualize CAPs and to understand the regulation of protein interaction with ceramide in CRPs.

10.
Nat Commun ; 10(1): 3078, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289268

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

11.
Stem Cell Res Ther ; 10(1): 172, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196174

RESUMO

BACKGROUND: Clinically, for stem cell-based therapy (SCBT), autologous stem cells are considered better than allogenic stem cells because of little immune rejection and no risk of communicable disease infection. However, severe maxillofacial bone defects restoration needs sufficient autologous stem cells, and this remains a challenge worldwide. Human gingival mesenchymal stem cells (hGMSCs) derived from clinically discarded, easily obtainable, and self-healing autologous gingival tissues, have higher proliferation rate compared with autologous bone marrow mesenchymal stem cells (hBMSCs). But for clinical bone regeneration purpose, GMSCs have inferior osteogenic differentiation capability. In this study, a TGF-ß signaling inhibitor SB431542 was used to enhance GMSCs osteogenesis in vitro and to repair minipig severe maxillofacial bone defects. METHODS: hGMSCs were isolated and cultured from clinically discarded gingival tissues. The effects of SB431542 on proliferation, apoptosis, and osteogenic differentiation of hGMSCs were analyzed in vitro, and then, SB431542-treated hGMSCs composited with Bio-Oss® were transplanted into immunocompromised mice subcutaneously to explore osteogenic differentiation in vivo. After that, SB431542-treated autologous pig GMSCs (pGMSCs) composited with Bio-Oss® were transplanted into circular confined defects (5 mm × 12 mm) in minipigs maxillary to investigate severe bone defect regeneration. Minipigs were sacrificed at 2 months and nude mice at 8 weeks to retrieve specimens for histological or micro-CT or CBCT analysis. Effects of SB431542 on TGF-ß and BMP signaling in hGMSCs were investigated by Western Blot or qRT-PCR. RESULTS: One micromolar of SB431542 treatment induced a robust osteogenesis of hGMSCs in vitro, without adverse effect on apoptosis and growth. In vivo, 1 µM SB431542 treatment also enabled striking osteogenesis of hGMSCs subcutaneously in nude mice and advanced new bone formation of pGMSCs in minipig maxillary bone defect model. In addition, SB431542-treated hGMSCs markedly increased bone-related proteins expression, and BMP2 and BMP4 gene expression. Conversely, SMAD3 protein-dependent TGF-ß signal pathway phosphorylation was decreased. CONCLUSIONS: Our study show that osteogenic differentiation of GMSCs treated with TGF-ß signaling inhibitor SB431542 was increased, and SB431542-treated autologous pig GMSCs could successfully repair minipig severe maxillofacial bone defects. This preclinical study brings about a promising large bone regeneration therapeutic potential of autologous GMSCs induced by SB431542 in clinic settings.

12.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(10): 1514-1524, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31176039

RESUMO

The sphingolipid ceramide regulates beta-oxidation of medium and long chain fatty acids in mitochondria. It is not known whether it also regulates oxidation of very long chain fatty acids (VLCFAs) in peroxisomes. Using affinity chromatography, co-immunoprecipitation, and proximity ligation assays we discovered that ceramide interacts with Hsd17b4, an enzyme critical for peroxisomal VLCFA oxidation and docosahexaenoic acid (DHA) generation. Immunocytochemistry showed that Hsd17b4 is distributed to ceramide-enriched mitochondria-associated membranes (CEMAMs). Molecular docking and in vitro mutagenesis experiments showed that ceramide binds to the sterol carrier protein 2-like domain in Hsd17b4 adjacent to peroxisome targeting signal 1 (PTS1), the C-terminal signal for interaction with peroxisomal biogenesis factor 5 (Pex5), a peroxin mediating transport of Hsd17b4 into peroxisomes. Inhibition of ceramide biosynthesis induced translocation of Hsd17b4 from CEMAMs to peroxisomes, interaction of Hsd17b4 with Pex5, and upregulation of DHA. This data indicates a novel role of ceramide as a molecular switch regulating interaction of Hsd17b4 with Pex5 and peroxisomal function.

13.
Medicine (Baltimore) ; 98(21): e15758, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124961

RESUMO

BACKGROUND: For cancer, it is common that there is usually a dysregulation of the long noncoding RNA regulator of reprogramming (LncRNA ROR). To illustrate the application of LncRNA ROR, which serves as the prognostic marker for the malignant tumors, it is of great importance to conduct a meta-analysis. METHODS: There were 3 databases being applied. The data used were collected before January 5, 2018. These 3 databases include the OVID, PubMed, and Science databse. To further explore the association between the expression and survival of LncRNA ROR, it calculated the 95% confidence intervals (CIs) and hazard ratios (HRs). Meanwhile, the odds ratios (ORs) have been calculated for the evaluation of the correlation between the pathological and expression parameters of LncRNA ROR. RESULTS: There were 8 researches participated by 720 patients. According to the HR, it has been implied that there was a high LncRNA ROR expression related with the weak disease-free survival (DFS) (HR = 3.48, 95% CI, 2.24-5.41) and overall survival (OS) (HR = 2.47, 95% CI, 1.76-3.47) among the cancer patients with none dramatic heterogeneity. There was also a correlation among lymph node metastasis (OR = 5.38, 95% CI, 2.21-13.12), high tumor stage (OR = 3.80, 95% CI, 1.95-7.41), and larger tumor size (OR = 4.43, 95% CI, 1.26-15.51). CONCLUSIONS: Thus, it can be predicted about the lymph node metastasis and high tumor stage, larger tumor size, DFS, and poor OS based on the high LncRNA ROR. This suggests that high LncRNA ROR can be used as a new indicator of poor prognosis in cancer.


Assuntos
Neoplasias/genética , Neoplasias/patologia , RNA Longo não Codificante/genética , Biomarcadores Tumorais , China , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Análise de Sobrevida , Carga Tumoral
14.
Cancer Med ; 8(5): 2074-2084, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30982232

RESUMO

Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non-BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients (P < 0.01). Some pathogenic mutations were detected in the patients' familiy members without the past history of tumor and 92 novel mutations were detected (31 on BRCA including 2 P, 16 LP, 13 VUS; 61 on non-BRCA1/2 including 9 LP, 52 VUS). The detection rate of BRCA1/2 mutations was higher in patients with three or more cancer family members than those with one or two. However, the difference was not statistically different. The results suggest that multigene panel testing can increase mutation detection rate for high-risk BC patients. Detailed family history can help to categorize new mutations.

15.
Int J Cardiol Heart Vasc ; 22: 205-209, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30963096

RESUMO

Background: Currently, there is no validated multivariate model to predict probability of coronary artery spasm (CAS) in patients with acute chest pain. Methods: A total of 976 consecutive patients with acute chest pain were enrolled. Patients were divided into two groups based on the presence of significant CAS. To adjust potential confounders, a multivariable analysis was performed and a clinical diagnostic score system for CAS was utilized for score derivation. Results: Multivariable analysis model selected 6 predictors for CAS. The integer score was assigned to each predictors: angina at rest alone (10 points), positive of hyperventilation test (8 points), allergies (3 points), asthma, ST-segment elevation and myocardial bridge (2 points each). We showed that the clinical diagnostic score system had accuracy in predicting CAS, as measured by the area under the curve (AUC), which was 0.952-0.966. The cut-off baseline value for the clinical diagnostic score system was set to 11-12 points with specificity of 91.0-93.3% and sensitivity of 90.7-92.9%, respectively. Conclusion: A clinical diagnostic score system was derived and validated as an accurate tool for estimating the pretest probability of CAS in patients with acute chest pain.

16.
Nat Commun ; 10(1): 1750, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988287

RESUMO

Auger recombination is the main non-radiative decay pathway for multi-carrier states of colloidal quantum dots, which affects performance of most of their optical and optoelectronic applications. Outstanding single-exciton properties of CdSe/CdS core/shell quantum dots enable us to simultaneously study the two basic types of Auger recombination channels-negative trion and positive trion channels. Though Auger rates of positive trion are regarded to be much faster than that of negative trion for II-VI quantum dots in literature, our experiments find the two rates can be inverted for certain core/shell geometries. This is confirmed by theoretical calculations as a result of geometry-dependent dielectric screening. By varying the core/shell geometry, both types of Auger rates can be independently tuned for ~ 1 order of magnitude. Experimental and theoretical findings shed new light on designing quantum dots with necessary Auger recombination characteristics for high-power light-emitting-diodes, lasers, single-molecular tracking, super-resolution microscope, and advanced quantum light sources.

17.
J Am Chem Soc ; 141(6): 2288-2298, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30649864

RESUMO

Mn2+-doped ZnSe nanocrystals (Mn:ZnSe d-dots) with high optical quality-high dopant emission quantum yield with monoexponential dopant-emission decay dynamics-enable systematic and quantitative studies of temperature- and Mn2+ concentration-dependent optical properties of the dopant emission, especially its relationship with magnetic coupling. While temperature-dependent steady-state and transient dopant emission of d-dots with dilute Mn2+ concentrations originated from isolated Mn2+ ions, and can be quantitatively treated as a result of exciton-phonon coupling of isolated paramagnetic emission centers. Dopant emission of d-dots with high Mn2+ concentrations (up to 50% of Zn2+ ions being replaced by Mn2+ ions in the core nanocrystals) are found solely related to magnetically coupled Mn2+ emission. Magnetic coupling effects on steady-state dopant emission of d-dots with high Mn2+ concentrations are much stronger than those observed for doped bulk semiconductors, which is found to follow a strong and universe shell-thickness dependence for the epitaxial ZnSe and/or ZnS shells of the d-dots. By exciting the magnetically coupled Mn2+ ions directly, dopant-emission of d-dots with high Mn2+ concentrations exhibit monoexponential decay dynamics. In addition to this emission channel, a minor channel with slightly longer decay lifetime appears when the host nanocrystals with high Mn2+ concentrations are excited, which is barely visible at room temperature and increases its fraction by decreasing temperature.

18.
J Dermatolog Treat ; 30(2): 200-205, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29863417

RESUMO

BACKGROUND: We aimed to explore potential molecular basis of keloid formation and response mechanism of keloid to hydrocortisone (HC). METHODS: Transcriptional profile of GSE7890 which contained five normal scars with no HC treatment (NNHC), four normal scars treated with HC (NHC), five keloids with no HC treatment (KNHC), and five keloids treated with HC (KHC) samples was downloaded to identify differentially expressed genes (DEGs). Based on DEGs, hierarchical cluster analysis and pathway enrichment analysis were performed. Then, identification of characteristic pathway was performed, followed by calculation of pathway deviation score. RESULTS: Compared to NNHC group, total 1603 DEGs in NHC group, 895 DEGs in KHC group, and 832 DEGs in KNHC group were identified. Hierarchical cluster analysis revealed these four groups could be well distinguished. Total three pathways included cytokine-cytokine receptor interactions were significantly different between KNHC and NNHC groups. Besides, MAPK signaling pathway, endocytosis, and apoptosis were selected between KHC and KNHC groups. Genes of vascular endothelial growth factor C (VEGFC), tenascin C (TNC), and jun proto-oncogene (JUN) were selected as important DEGs in KHC, KNHC, and NHC groups, respectively. CONCLUSIONS: VEGF and TNC were, respectively, involved in KHC and KNHC in the mechanism of focal adhesion. JUN might be a potential molecular marker related to normal scar.


Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica , Hidrocortisona/farmacologia , Queloide/tratamento farmacológico , Análise por Conglomerados , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Tenascina/genética , Fator C de Crescimento do Endotélio Vascular/genética
19.
Genomics ; 111(6): 1566-1573, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30439482

RESUMO

Constitutive activation of FGFR1 as a result of chromosome translocations is responsible for the development of a hematopoietic stem cell disorder that progresses to AML. We have developed a syngeneic mouse model of BCR-FGFR1 driven AML and used RNASeq to define gene expression signatures associated with disease progression. The development of the leukemic stem cells (LSC) is associated with a profound downregulation of specific transcription factors that normally maintain stem cell quiescence as well as cell adhesion and motility gene sets related to confinement to the stem cell niche. A prominent feature of the LSCs is the upregulation of genes involved in T-cell function, activation, migration and development. Despite this apparent T-cell priming in the LSCs, however, the majority of these genes are subsequently inactivated in the leukemic blast cells that derive from them. These studies provide insights into the molecular etiology of development and progression of FGFR1 driven AML.

20.
Genesis ; 57(2): e23268, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30489685

RESUMO

Constitutional mutations in Leucine-rich glioma inactivated 1 (LGI1) predispose to an autosomal dominant epilepsy syndrome in humans and germline inactivation of LGI1 in mice leads to early onset seizures. LGI1 is highly expressed in the regions involved in neuronal stem cell generation and migration and detailed analysis of the brains in these mice reveals a subtle cortical dysplasia characterized by hypercellularity in the outer cortical layers. To investigate the cellular origin for this cortical dysplasia, we created mice that allow cell-specific, conditional inactivation of LGI1. Exons 3-4, which contain critical motifs for LGI1 function, were targeted for deletion and, using a CMV-cre mouse strain, global inactivation of LGI1 led to early onset seizures and the same cortical dysplasia seen in the constitutionally null mice. Similarly, inactivation of LGI1 in cells expressing Nestin, expressed primarily in neuronal precursor cells, led to early onset seizures and cortical dysplasia. In contrast, targeting inactivation of LGI1 in cells expressing Gfap, Camk2a, and parvalbumin, did not lead to cortical dysplasia. This strain of mouse, therefore, allows for a more refined investigation of the cell types involved in the cortical dysplasia seen following inactivation of LGI1 and potentially a better understanding of the molecular mechanisms behind LGI1-induced epilepsy.


Assuntos
Malformações do Desenvolvimento Cortical/genética , Células-Tronco Neurais/metabolismo , Proteínas/genética , Animais , Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Mutação com Perda de Função , Camundongos
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