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1.
Inorg Chem ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017542

RESUMO

The directing effect of coordinating ligands in the formation of uranium molecular complexes has been well established, but the role of counterions in metal-ligand interactions remains ambiguous and requires further investigation. In this work, we describe the targeted isolation, through the choice of alkali-metal ions, of a family of tetravalent uranium sulfates, showing the influence of the overall topology and, unexpectedly, the UIV nuclearity upon the inclusion of such countercations. Analyses of the structures of uranium(IV) oxo/hydroxosulfate oligomeric species isolated from consistent synthetic conditions reveal that the incorporation of Na+ and Rb+ promotes the crystallization of 0D discrete clusters with a hexanuclear [U6O4(OH)4(H2O)4]12+ core, whereas the larger Cs+ ion allows for the isolation of a 2D-layered oligomer with a less condensed trinuclear [U3(O)]10+ center. This finding expands the prevalent view that counterions play an innocent role in molecular complex synthesis, affecting only the overall packing but not the local oligomerization. Interestingly, trends in nuclearity appear to correlate with the hydration enthalpies of alkali-metal cations, such that the alkali-metal cations with larger hydration enthalpies correspond to more hydrated complexes and cluster cores. These findings afford new insights into the mechanism of nucleation of UIV, and they also open a new path for the rational design and synthesis of targeted molecular complexes.

2.
Life Sci ; 245: 117356, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991181

RESUMO

AIMS: NPY-Y1R plays an important role in dietary regulation. Although germline knockdown of NPY-Y1R in mice alleviates high-fat-diet-induced obesity and increases CPT1α levels in the liver, the role of the Y1 receptor in specific tissues has not been studied. MAIN METHODS: MCD diet is the most widely used method to establish a model of lean NASH in a short time. We therefore evaluated the role of liver NPY-Y1R in NASH progression. KEY FINDINGS: In mice with liver-specific knockout of NPY-Y1R (LivKO) and wild-type control littermates fed MCD diet for 4 weeks, NPY-Y1R deficiency significantly decreased body and liver weight. Moreover, NPY-Y1R deletion protected mice against hepatic steatosis and injury. LivKO decreased TG, TC, and FFA levels in the liver and alanine aminotransferase activity in plasma. To clarify the mechanism, we evaluated the key enzymes involved in triglyceride hydrolase and fatty-acid oxidase. Expression of ATGL, CPT1α, and ACO was significantly increased in LivKO mice, whereas expression of fatty-acid synthase was significantly decreased. mRNA expression analysis revealed a marked reduction of genes involved in de-novo lipogenesis and monosaturated fatty-acid synthesis, including sterol-regulatory element-binding protein 1c and fatty-acid synthase. Moreover, liver injury-related factors were significantly decreased in LivKO mice, such as TNF-α, inducible nitric oxide synthase, and MCP-1. Thus, NPY-Y1R deficiency in the liver alleviates lipid deposition and injury. However, NPY-Y1R did not affect inflammation and fibrosis. SIGNIFICANCE: NPY-Y1R deficiency in the liver directly suppresses not only hepatic steatosis, but also liver injury, and thus provides a treatment option for NASH.

3.
Inorg Chem ; 59(1): 943-955, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31815447

RESUMO

Template synthesis is one of the most feasible ways to explore new uranyl compounds with intriguing structures and properties. Here we demonstrate the preparation of six novel "sandwichlike" uranyl coordination polymers (UCPs) based on two-dimensional uranyl-terephthalate acid (H2TP) networks using CBn (n = 5, 6, 8) as template ligands in the presence of different cations (Na+, K+, Cs+, or H2N(CH3)2+). Compound 1 ([UO2(TP)2][Na2(CB5)(H2O)](H2O)5) is composed of layered uranyl-TP networks with the complex of CB5 and sodium cations as template ligands. In compound 2 ([(UO2)2(TP)3]2(CB6)(H2O)10), CB6 located between uranyl-TP networks contacts them by π-π interactions and hydrogen bonds. Compound 3 ([(UO2)2(TP)3]2[Na2(H2O)10(CB6)]) is the same as compound 2 except for sodium cations bonding with CB6. Similarly in compound 4 ([(UO2)2(TP)3][Cs(H2O)3(CB6)]), CB6 is a capsulelike structure capped with two cesium cations and interacts with uranyl-TP networks through π-π and C-H···π interactions. Compound 5 ([(UO2)2(TP)3(HCOO)2][K(H2O)2(CB5)]2[H2N(CH3)2]2(CB6)(H2O)6) consists of both templates of CB6 and CB5 in which each CB5 is capped with one potassium cation while the H2N(CH3)2+ cation is held at CB6 portals. In compound 6 ([(UO2)2(TP)3]2[UO2(TP)2(H2O)2][Cs(CB8)3(H2O)4](H2O)16), CB8 ligands are connected by cesium cations to form a triangle motif and are further located between the uranyl-TP networks as template agents. All of the 2D layered structures with free CBn or cation-anchored CBn intercalate into the laminates of uranyl-terephthalate and shows a cucurbituril-mediated structural evolution. The regulating role of CBn as structure-directing template agents for the construction of layered UCPs through outer-surface interactions with layers of uranyl terephthalate is demonstrated, especially for the case of CB6 with contractive interlayer spacing.

4.
Cancer Sci ; 111(1): 59-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729097

RESUMO

Low vitamin D status is associated with progression in patients with renal cell carcinoma (RCC). The present study found that vimentin, a mesenchymal marker, was accordingly upregulated, and E-cadherin, an epithelial marker, was downregulated in RCC patients with low vitamin D status. Thus, we investigated the effects of calcitriol or vitamin D3, an active form of vitamin D, on epithelial-mesenchymal transition (EMT) in RCC cells. RCC cells were treated by two models. In model 1, three RCC cell lines, ACHN, 786-O and CAKI-2, were incubated with either LPS (2.0 µg/mL) or transforming growth factor (TGF)-ß1 (10 ng/mL) in the presence or absence of calcitriol (200 nmol/L). In model 2, two RCC cell lines, ACHN and CAKI-2, were incubated with calcitriol (200 nmol/L) only. Calcitriol inhibited migration and invasion not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated RCC cells. Moreover, calcitriol suppressed E-cadherin downregulation and vimentin upregulation not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated ACHN and CAKI-2 cells. Calcitriol attenuated LPS-induced upregulation of MMP-2, MMP-7, MMP-9, MMP-26 and urokinase-type plasminogen activator (u-PA) in ACHN cells. In addition, calcitriol blocked TGF-ß1-induced nuclear translocation of ZEB1, Snail and Twist1 in ACHN and CAKI-2 cells. Mechanistically, calcitriol suppressed EMT through different signaling pathways: (i) calcitriol suppressed Smad2/3 phosphorylation by reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-ß1-stimulated RCC cells; (ii) calcitriol inhibited signal transducer and activator of transcription (STAT)3 activation in LPS-stimulated RCC cells; (iii) calcitriol inhibited ß-catenin/TCF-4 activation by promoting integration of VDR with ß-catenin in TGF-ß1-unstimulated RCC cells. Taken together, calcitriol inhibits migration and invasion of RCC cells partially by suppressing Smad2/3-, STAT3- and ß-catenin-mediated EMT.


Assuntos
Calcitriol/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Adulto , Idoso , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Renais/metabolismo , Masculino , Metaloendopeptidases/metabolismo , Pessoa de Meia-Idade , Fator de Transcrição STAT3/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , beta Catenina/metabolismo
5.
CNS Neurosci Ther ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31880085

RESUMO

AIMS: Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated. METHODS: Twenty-four C57BL/6J mice were divided into four groups: a control group; a risperidone-treated group; a lorcaserin-treated group; and a combined risperidone + lorcaserin-treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes post-treatment for determination of c-fos activity. In addition, brains of NPY-GFP mice treated with or without risperidone were collected to perform colocalization of NPY and c-fos, as well as NPY and 5-HT2c receptor using immunohistochemistry. RESULTS: There was significantly elevated c-fos expression in the hypothalamic arcuate nucleus (Arc) of risperidone-treated mice. More than 68% c-fos-positive neurons were NPY-expressing neurons. Furthermore, in situ hybridization revealed that Arc NPY mRNA expression was significantly increased in the risperidone-treated group compared with control group. Moreover, we identified that 95% 5-HT2c receptors were colocalized with NPY positive neurons, and increased Arc NPY mRNA expression induced by risperidone was markedly reduced by cotreatment with lorcaserin, a specific 5-HT2c receptor agonist. CONCLUSION: Our findings provide critical insight into the mechanisms underlying antipsychotic-induced obesity, which may assist the development of therapeutic strategies to address metabolic side effects of risperidone.

6.
Sci Rep ; 9(1): 16719, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723229

RESUMO

Low vitamin D status is associated with an increased risk of renal cell carcinoma (RCC). This study investigated the association of vitamin D status with serum C-reactive protein (CRP) and adhesion molecules among RCC patients. Fifty newly diagnosed RCC patients and 100 age- and sex-matched controls were recruited. As expected, serum 25(OH)D level was lower in RCC patients than in controls. By contrast, serum levels of CRP, an inflammatory molecule, and ICAM, LAMA4 and EpCAM, three adhesion molecules, were higher in RCC patients than in controls. All RCC patients were divided into two groups: H-VitD (>20 ng/ml) or L-VitD (<20 ng/ml). Interestingly, the levels of serum CRP and all adhesion molecules were higher in RCC patients with L-VitD than those with H-VitD. Nuclear vitamin D receptor (VDR) was downregulated and nuclear factor kappa B (NF-κB) was activated in cancerous tissues. The in vitro experiments found that VitD3 suppressed NF-κB activation and adhesion molecules in RCC cells. Moreover, VitD3 suppressed NF-κB through reinforcing physical interaction between VDR and NF-κB p65 subunit in RCC cells. These results provide a mechanistic explanation for the association among low vitamin D status, local inflammation and increased expression of adhesion molecules among RCC patients.

7.
Steroids ; 150: 108445, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295461

RESUMO

Low vitamin D status has been associated with increased risks of renal cell carcinoma (RCC). This study aimed to analyze the link between low vitamin D status and interleukin (IL)-6/STAT3 hyper-activation in clear cell RCC (ccRCC) patients. Forty-three newly diagnosed ccRCC patients and 86 age- and sex-matched controls were recruited. The association between low vitamin D status and IL-6/STAT3 hyper-activation was analyzed. Proliferation makersand STAT3 signal were evaluated. As expected, serum IL-6 level was higher in ccRCC patients than in controls. Moreover, serum IL-6 level was reversely correlated with serum 25(OH)D in ccRCC patients but not in controls. In addition, STAT3 signaling was hyper-activated in cancerous tissue. CcRCC patients were divided into three groups according to serum 25(OH)D level: vitamin D sufficiency (VitD-S, ≥30 ng/ml), vitamin D insufficiency (VitD-I, ≥20 and <30 ng/ml) or vitamin D deficiency (VitD-D, <20 ng/ml). Serum IL-6 was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. Cancerous pSTAT3 level was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The number of pSTAT3+ nuclei in cancerous tissue was more in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The expressions of cancerous PCNA, cyclin D1 and Ki-67, three markers of proliferation, were higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The in vitro experiments showed that active vitamin D3 inhibited LPS-induced STAT3 phosphorylation in ACHN cells. Our results provide evidence that low vitamin D status is correlated with hyper-activation of cancerous IL-6/STAT3 and proliferation in ccRCC patients.

8.
Aging (Albany NY) ; 11(10): 3376-3391, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147526

RESUMO

MircoRNA-335 (miR-335) has been reported as a significant cancer-associated microRNA, which was often epigenetically silenced and acted as a tumor suppressor gene in diverse human solid tumors. Conversely, recent studies show that miR-335 overexpression was identified in both adult and pediatric acute myeloid leukemia (AML), suggesting that it might play an oncogenic role of miR-335 in AML. However, the role of miR-335 during leukemogenesis remains to be elucidated. MiR-335/ID4 expression was detected by real-time quantitative PCR and/or western blot. Survival analysis was performed to explore the association between miR-335/ID4 expression and the prognosis, and further validated by public databases. Gain-of-function experiments determined by cell proliferation, apoptosis, and differentiation were conducted to investigate the biological functions of miR-335/ID4. Herein, we found that miR-335 expression, independent of its methylation, was significantly increased and negatively correlated with reduced ID4 expression in AML. Moreover, aberrant miR-335/ID4 expression independently affected chemotherapy response and leukemia-free/overall survival in patients with AML. Gain-of-function experiments in vitro showed the oncogenic role of miR-335 by affecting cell apoptosis and proliferation in AML, and could be rescued by ID4 restoration. Mechanistically, we identified and verified that miR-335/ID4 contributed to leukemogenesis through activating PI3K/Akt signaling pathway. Collectively, aberrant miR-335/ID4 expression was an independent prognostic biomarker in AML. MiR-335/ID4 dysregulation facilitated leukemogenesis through the activation of PI3K/Akt signaling pathway.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 646-651, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204912

RESUMO

OBJECTIVE: To investigate the clinical significance of SCIN gene expression and promoter methylation in patients with chronic myeloid leukemia (CML). METHODS: Real-time quantitative PCR was used to detect the expression level of SCIN in mononucleatr cells of bone marrow samples from 64 CML patients and 37 controls. The methylation levels of SCIN promoter in 65 patients with CML and 29 controls were detected by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR. RESULTS: The expression level of SCIN in CML patients was significantly down-regulated (P<0.05), compared with the control group. The down-regulation rate of SCIN expression in CML patients at chronic phase, accelerated phase and blast crisis was 61%, 67% and 75%, respectively. Spearman correlation analysis showed that the expression level of SCIN negatively correlated with the transcript level of BCR-ABL1 (R=-0.315, P<0.05). However, there was no significant difference in clinical parameters such as sex, age, white blood cell count, hemoglobin level, platelet count, chromosome, CML staging and BCL-ABL1 transcript level between low and high SCIN expression groups of CML patients (P>0.05). No significant difference in methylation of SCIN promoter between CML patients and controls, and no correlation between SCIN expression and promoter methylation were observed (P>0.05). CONCLUSION: The SCIN expression is down-regulated in CML patients, which may relate with the pathogenesis that is, BCR-ABL1 fusion gene induces CML tumorigenesis. The down-regulation of SCIN expression may relate with the progression of CML.


Assuntos
Metilação de DNA , Gelsolina/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva , Crise Blástica , Regulação para Baixo , Proteínas de Fusão bcr-abl , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Regiões Promotoras Genéticas
10.
Stem Cells ; 37(10): 1331-1343, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31233254

RESUMO

Endothelial progenitor cells (EPCs) contribute to blood vessel formation. Canonical Wnt signaling plays an important role in physiological and pathological angiogenesis and EPC fate regulation. However, the mechanism for Wnt signaling to regulate EPC fate in neovascularization (NV) has not been clearly defined. Here, we showed that very low-density lipoprotein receptor knockout (Vldlr -/- ) mice, a model of ocular NV induced by Wnt signaling overactivation, have increased EPC numbers in the bone marrow, blood, and retina, as well as an elevated mitochondrial membrane potential indicating higher mitochondrial function of EPCs in the circulation. Isolated EPCs from Vldlr -/- mice showed overactivated Wnt signaling, correlating with increased mitochondrial function, mass, and DNA copy numbers, compared with WT EPCs. Our results also demonstrated that Wnt signaling upregulated mitochondrial biogenesis and function, while inhibiting glycolysis in EPCs, which further decreased EPC stemness and promoted EPCs to a more active state toward differentiation, which may contribute to pathologic vascular formation. Fenofibric acid, an active metabolite of fenofibrate, inhibited Wnt signaling and mitochondrial function in EPCs and decreased EPC numbers in Vldlr -/- mice. It also decreased mitochondrial biogenesis and reactive oxygen species production in Vldlr -/- EPCs, which may be responsible for its therapeutic effect on diabetic retinopathy. These findings demonstrated that Wnt signaling regulates EPC fate through metabolism, suggesting potential application of the EPC metabolic profile as predictor and therapeutic target for neovascular diseases. Stem Cells 2019;37:1331-1343.

11.
Onco Targets Ther ; 12: 3295-3304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118680

RESUMO

Background: Altered expression of the BCL-2 family member MCL-1 has been linked to the progression and outcome of various malignancies. Recently, MCL-1 inhibitor S63845 was reported to kill MCL-1-dependent cancer cells and has potential value in clinical application. Purpose: Herein, we reported MCL-1 expression pattern in Chinese de novo acute myeloid leukemia (AML) and its impact on prognosis and may provide theoretical basis for AML patients using MCL-1 inhibitor in clinics. Real-time quantitative PCR was carried out to detect the transcript of MCL-1 in AML patients. Results: MCL-1 expression was significantly up-regulated in AML compared with controls (P=0.042). We divided the patients into two groups (higher and lower expression of MCL-1) based on the median level. Among both non-acute promyelocytic leukemia (APL) and cytogenetically normal AML (CN-AML), patients with higher expression of MCL-1 correlated with lower complete remission (CR) rate (P=0.031 and 0.004, respectively) and shorter overall survival (OS) time (P=0.008 and 0.004, respectively) compared with those with lower expression of MCL-1. Meanwhile, Cox regression analyses revealed that overexpression of MCL-1 acted as an independent risk factor for OS in non-APL patients and CN-AML patients (P=0.011 and 0.045, respectively). In follow-up patients, MCL-1 expression level decreased after CR compared with newly diagnosis time (P=0.020) and increased after relapse (P=0.004). Conclusion: Our findings suggest that higher expression of MCL-1 predicts poor prognosis and can be used for disease monitoring.

12.
Oxid Med Cell Longev ; 2019: 1897316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019650

RESUMO

Background: Cellular stress is involved in ischemia/reperfusion- (I/R-) induced acute kidney injury (AKI). This study is aimed at investigating the effects of pretreatment with cholecalciferol on renal oxidative stress and endoplasmic reticulum (ER) stress during I/R-induced AKI. Methods: I/R-induced AKI was established by cross-clamping renal pedicles for 90 minutes and then reperfusion. In the Chol + I/R group, mice were orally administered with three doses of cholecalciferol (25 µg/kg) at 1, 24, and 48 h before ischemia. Renal cellular stress and kidney injury were measured at different time points after reperfusion. Results: I/R-induced AKI was alleviated in mice pretreated with cholecalciferol. In addition, I/R-induced renal cell apoptosis, as determined by TUNEL, was suppressed by cholecalciferol. Additional experiment showed that I/R-induced upregulation of renal GRP78 and CHOP was inhibited by cholecalciferol. I/R-induced renal IRE1α and eIF2α phosphorylation was attenuated by cholecalciferol. Moreover, I/R-induced renal GSH depletion, lipid peroxidation, and protein nitration were blocked in mice pretreated with cholecalciferol. I/R-induced upregulation of renal NADPH oxidases, such as p47phox, gp91phox, and nox4, was inhibited by cholecalciferol. I/R-induced upregulation of heme oxygenase- (HO-) 1, gshpx and gshrd, was attenuated in mice pretreated with cholecalciferol. Conclusions: Pretreatment with cholecalciferol protects against I/R-induced AKI partially through suppressing renal cellular stress response.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/patologia , Colecalciferol/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/complicações , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Glutationa/metabolismo , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , NADPH Oxidases/metabolismo , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
13.
Chem Asian J ; 14(11): 1970-1976, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-30920761

RESUMO

The understanding of crystal stepwise transformation is very important to enclose the "black box" in the preparation of crystal materials. In this work, different structural intermediates were isolated prior to the formation of the final alkali earth coordination polymers (CPs) during the preparation of three pairs of alkali earth CPs through solvothermal method and convenient oil-bath reactions. Single crystal X-ray diffraction analysis demonstrated the structural transformation from a 0 D to 1 D inorganic connectivity for the Ca-CPs and Sr-CPs, but a 1 D to 0 D inorganic connectivity for Ba-CPs, involving the breakage/formation of chemical bonds in the reaction solutions. Further analyses indicated that these two different structural transformation pathways are determined by the deprotonation of organic acid, competitive balance between the inorganic and organic connectivity, and the twist of the linker. FT-IR spectra, thermogravimetric and luminescence behaviors agree with their structural characteristics.

14.
Int Immunopharmacol ; 69: 235-244, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30738993

RESUMO

Several epidemiological reports demonstrated that vitamin D deficiency elevated risk of preterm delivery. We investigate the effects of oral cholecalciferol (VD3) supplementation on lipopolysaccharide (LPS)-induced preterm delivery. Pregnant mice were randomly assigned to either oral VD3 (25 µg/kg) or corn oil once daily from gestational day (GD)13 to GD15, and were intraperitoneally injected with either LPS (200 µg/kg) or normal saline on GD15. As expected, LPS was effective in inducing preterm delivery and fetal death. LPS-induced preterm delivery and fetal death were alleviated in VD3-pretreated mice. LPS-induced down-regulation of genes for placental progesterone biosynthetic enzymes was blocked in VD3-pretreated mice. LPS-induced reduction of serum progesterone was correspondingly attenuated by VD3. Although oral VD3 had no effect on estradiol production, it attenuated LPS-induced up-regulation of placental ERß in mice. LPS-induced placental COX-2 up-regulation and serum PGF2α elevation were alleviated in VD3-pretreated mice. Additionally, LPS-evoked elevations of the placental Tnfα, Il1ß, Mcp1 and Mip2 mRNAs were attenuated by VD3. VD3 promoted placental vitamin D receptor nuclear translocation and simultaneously alleviated LPS-induced nuclear translocation of NF-κB p65 and p50 subunits. These results provide evidence that oral VD3 supplementation alleviates LPS-induced preterm delivery and fetal demise partially through regulating placental steroid hormones and prostaglandins.


Assuntos
Colecalciferol/uso terapêutico , Suplementos Nutricionais , Placenta/metabolismo , Nascimento Prematuro/dietoterapia , Receptores de Calcitriol/metabolismo , Administração Oral , Animais , Estradiol/metabolismo , Feminino , Humanos , Inflamação , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Progesterona/metabolismo , Prostaglandinas/metabolismo
15.
Acta Crystallogr E Crystallogr Commun ; 75(Pt 1): 68-70, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30713736

RESUMO

In the title organic salt, C17H20F2N3O3 +·C8H4FO4 -, proton transfer leads to one protonated lomefloxacin mol-ecule (HLf+) and one 3-carb-oxy-5-fluoro-benzoate (5-F-Hip-) anion in the asymmetric unit. The HLf+ cation is bent, with a dihedral angle of 38.3 (1)° between the quinoline ring and the piperazinium moiety. In the crystal, two kinds of N-H⋯O and O-H⋯O hydrogen-bonded chains cross-link each other to produce a three-dimensional network structure that is additionally stabilized by weak C-H⋯O and C-H⋯F hydrogen bonds, as well as π-π inter-actions. The methyl group attached to the piperazinium ring is disordered over two sets of sites [refined ratio: 0.645 (5):0.335 (5)], indicating the presence of both enanti-omers of the cation in the structure.

16.
J Cell Physiol ; 234(6): 9438-9446, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30317626

RESUMO

The current study was aimed to investigate integrin beta-like 1 (ITGBL1) methylation pattern and its clinical relevance in patients with acute myeloid leukemia (AML). Real-time methylation-specific polymerase chain reaction (PCR; RQ-MSP) and bisulfite sequencing PCR (BSP) were performed to detect the methylation of ITGBL1 promoter. Real-time quantitative PCR (RT-qPCR) was performed to analyze ITGBL1 transcript level. The results showed that ITGBL1 methylation level in 131 patients with AML was significantly higher than 29 controls (p < 0.001). The ITGBL1-hypermethylated group tended to have a higher bone marrow (BM) blasts ( p = 0.076). Meanwhile, ITGBL1-hypermethylated patients tended to have a lower complete remission (CR) rate ( p = 0.102). ITGBL1-hypermethylated patients had significantly shorter overall survival (OS) and leukemia-free survival (LFS) than ITGBL1 hypomethylated patients in whole AML cohort ( p = 0.009 and 0.043, respectively) and patients with nonacute promyelocytic leukemia (APL ; p = 0.023 and 0.039, respectively). Multivariate analysis confirmed that the ITGBL1 methylation served as an independent prognostic factor in both patients with whole-cohort AML ( p = 0.030) and patients with non-APL ( p = 0.020). Furthermore, the ITGBL1 methylation level was significantly decreased in follow-up AML patients who achieved complete remission after induction therapy ( P = 0.001). ITGBL1 methylation negatively correlated with ITGBL1 expression in patients with AML ( R = -0.328, p = 0.008). Moreover, demethylation of ITGBL1 could increase the ITGBL1 expression in the K562 leukemic cell line ( p < 0.05). In conclusion, the ITGBL1 hypermethylation is a potential biomarker for predicting prognosis and monitoring disease status in patients with AML.

17.
BMC Cancer ; 18(1): 1277, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572846

RESUMO

BACKGROUND: Ventana ALK (D5F3) screening of anaplastic lymphoma kinase (ALK) gene rearrangement in tissue specimens has been approved by US FDA (Food and Drug Administration) to select treatment for non-small-cell lung carcinoma (NSCLC). However, tumor tissues are often not readily obtainable, and cytology specimens and may be the only tumor material available for diagnosis and molecular marker analysis. In this study, we evaluated the feasibility of ALK immunocytochemistry (ICC) on ThinPrep slides and determined a suitable scoring system for interpretation of the results. METHODS: One hundred twenty-one fine-needle aspirate (FNA) specimens from metastatic lesions of NSCLC were analyzed. ALK rearrangement was detected on ThinPrep cytology slides using the Ventana immunocytochemistry ALK-D5F3 system, which adopts two scoring systems for interpretation of the ICC results. The results were subsequently confirmed by reverse transcription polymerase chain reaction (RT-PCR) analysis and fluorescence in situ hybridization (FISH). RESULTS: Among the 121 ICC specimens, 16 that were considered ALK-positive by either scoring system were referred for PCR analysis. Among the ALK ICC-negative cases, 33 had correlated FISH ALK results. A total of 49 specimens that exhibited either a positive or negative ICC result with a correlated ALK status were analyzed statistically. ICC results showed a high concordance rate with the results of PCR/FISH analysis. The sensitivity and specificity of ALK ICC by the binary scoring algorithm were 68.75 and 96.97%, respectively. These values increased to 93.75 and 96.97%, respectively, when interpreted by the semiquantified interpretation system. CONCLUSIONS: ALK ICC analysis on ThinPrep slides is a reliable ALK testing method, and the semiquantified interpretation system on cytology specimens is recommended rather than the binary scoring algorithm on tissue specimens.


Assuntos
Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Citodiagnóstico , Adenocarcinoma , Idoso , Quinase do Linfoma Anaplásico/isolamento & purificação , Biópsia por Agulha Fina , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Rearranjo Gênico/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
18.
Eur J Pharmacol ; 838: 60-68, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30196109

RESUMO

It is increasingly recognized that farnesoid X receptor (FXR) has anti-inflammatory and antioxidant activities. The present study investigated the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, on renal inflammation and oxidative stress in a model of sepsis-induced acute kidney injury. All mice except controls were intraperitoneally injected with lipopolysaccharide (LPS, 2.0 mg/kg). In the OCA + LPS group, mice were orally pretreated with three doses of OCA (5 mg/kg) at 48, 24 and 1 h before LPS injection. Interestingly, OCA pretreatment alleviated LPS-induced renal dysfunction and pathological damage. Moreover, OCA pretreatment repressed renal inflammatory cytokines and chemokines during LPS-induced acute kidney injury. In addition, OCA blocked nuclear translocation of nuclear factor kappa B (NF-κB) p65 and p50 subunits in tubular epithelial cells of renal cortex. Additional experiment showed that OCA pretreatment attenuated LPS-induced renal glutathione depletion, lipid peroxidation and protein nitration. Moreover, OCA pretreatment inhibited the upregulation of renal NADPH oxidase and inos genes during LPS-induced acute kidney injury. In conclusion, OCA pretreatment protects against sepsis-induced acute kidney injury through inhibiting renal inflammation and oxidative stress. These results provide evidence for roles of FXR as an important regulator of inflammation and oxidative stress in the kidney.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Ácido Quenodesoxicólico/análogos & derivados , Nefrite/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/agonistas , Lesão Renal Aguda/imunologia , Lesão Renal Aguda/patologia , Administração Oral , Animais , Ácido Quenodesoxicólico/farmacologia , Ácido Quenodesoxicólico/uso terapêutico , Modelos Animais de Doenças , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nefrite/imunologia , Nefrite/patologia , Receptores Citoplasmáticos e Nucleares/metabolismo
19.
Chemistry ; 24(63): 16766-16769, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30203453

RESUMO

Uranyl-organic frameworks (UOFs) have recently been the object of many research endeavors due to the unique coordination mode of uranyl ions and their attractive physicochemical properties. Here, a new (3,4)-connected UOF (U-IHEP-4) assembled from uranyl and porphyrin ligand tetrakis(4-carboxyphenyl)porphyrin (H4TCPP) is reported, which represents the first case of actinide porphyrinic MOFs. Adsorption experiments in DMF solution demonstrated that U-IHEP-4 selectively adsorbs positively charged dyes, which is in line with its negatively charged framework and large pore volume ratio (90 %). Remarkably, U-IHEP-4 exhibited high catalytic activity for the dehydrogenation of N-heterocycles to synthesize the corresponding aromatic heterocycles and it can be used as an efficient heterogeneous catalyst.

20.
Mol Med Rep ; 18(4): 3923-3931, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30106124

RESUMO

Cold exposure is considered to be a form of stress and has various adverse effects on the body. The present study aimed to investigate the effects of chronic daily cold exposure on food intake, body weight, serum glucose levels and the central energy balance regulatory pathway in mice fed with a high­fat diet (HFD). C57BL/6 mice were divided into two groups, which were fed with a standard chow or with a HFD. Half of the mice in each group were exposed to ice­cold water for 1 h/day for 7 weeks, while the controls were exposed to room temperature. Chronic daily cold exposure significantly increased energy intake, body weight and serum glucose levels in HFD­fed mice compared with the control group. In addition, 1 h after the final cold exposure, c­fos immunoreactivity was significantly increased in the central amygdala of HFD­fed mice compared with HFD­fed mice without cold exposure, indicating neuronal activation in this brain region. Notably, 61% of these c­fos neurons co­expressed the neuropeptide Y (NPY), and the orexigenic peptide levels were significantly increased in the central amygdala of cold­exposed mice compared with control mice. Notably, cold exposure significantly decreased the anorexigenic brain­derived neurotropic factor (BDNF) messenger RNA (mRNA) levels in the ventromedial hypothalamic nucleus and increased growth hormone releasing hormone (GHRH) mRNA in the paraventricular nucleus. NPY­ergic neurons in the central amygdala were activated by chronic cold exposure in mice on HFD via neuronal pathways to decrease BDNF and increase GHRH mRNA expression, possibly contributing to the development of obesity and impairment of glucose homeostasis.


Assuntos
Temperatura Baixa , Glucose/metabolismo , Homeostase , Obesidade/metabolismo , Obesidade/patologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Tonsila do Cerebelo/metabolismo , Animais , Peso Corporal , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dieta Hiperlipídica , Ingestão de Alimentos , Proteínas de Fluorescência Verde/metabolismo , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neuropeptídeo Y/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estresse Fisiológico , Núcleo Hipotalâmico Ventromedial/metabolismo
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