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1.
Clin Exp Allergy ; 54(2): 109-119, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38011856

RESUMO

BACKGROUND: Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early-life viral wheezing remain uncertain. METHODS: To investigate a causal relationship between early-life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity. RESULTS: RSV infection of neonatal BALB/c mice at 5 and 15 days of age induced robust airway eosinophilia, increased pulmonary CD4+ IL-13+ and CD4+ IL-5+ cells, elevated levels of IL-13 and IL-5 and increased airway mucus at 20 days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised. CONCLUSIONS: The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations.


Assuntos
Asma , Eosinofilia , Infecções por Vírus Respiratório Sincicial , Humanos , Pré-Escolar , Animais , Camundongos , Recém-Nascido , Infecções por Vírus Respiratório Sincicial/complicações , Interleucina-13 , Modelos Animais de Doenças , Interleucina-5 , Pulmão , Asma/etiologia , Eosinofilia/etiologia , Camundongos Endogâmicos BALB C
2.
Chemistry ; 30(4): e202302671, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-37920946

RESUMO

Organic ferroelectrics have received a great deal of interest due to their exclusive properties. However, organic ferroelectrics have not been fully explored, which hinders their practical application. Here, we presented a novel metal-free organic molecular ferroelectric [4-MCHA][ClO4 ] (1) (4-MCHA=trans-4-methylcyclohexylamine), which exhibits an above-room-temperature of 328 K. Strikingly, the single crystal structure analysis of 1 shows that the driving force of phase transition is related to the interesting chair-boat conformation change of 4-MCHA cation, in addition to the order-disorder transition of ClO4 - anion. Using piezoelectric response force microscopy (PFM), the presence of domains and the implemented polarization switching were clearly observed, which explicitly determined the presence of room-temperature ferroelectricity of 1. As far as we know, the ferroelectric phase transition mechanism attributed to the conformational change in a trans isomeric cation is very rare. This research enriched the path of designing ferroelectric materials and smart materials.

3.
Inorg Chem ; 63(1): 184-190, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38113285

RESUMO

Organic-inorganic hybrid metal halides have attracted significant attention in recent years due to their excellent optoelectronic properties and potential applications in solar cells. Herein, the organic-inorganic hybrid molecule [N,N-dimethyl-1,3-propanediamine]SbBr5 (1) was synthesized by reacting a long-chain organic diamine N,N-dimethyl-1,3-propanediamine with SbBr3 as a metal halide precursor in HBr aqueous solution. Compound 1 possesses a one-dimensional chainlike structure with the second-harmonic generation switch and two continuous phase transitions above room temperature. The band gap of compound 1 is about 2.62 eV, exhibiting a semiconductive property, which may have important implications for the development of new optoelectronic devices.

4.
Inorg Chem ; 63(2): 1337-1346, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38153815

RESUMO

Reactions of a chiral and quasi-spherical molecule [1S,4S-2,5-2.2.1-H2dabch]I2 (1) with alkali metal halide MX (M = Na, K, Cs; X = Cl, Br) at room temperature produced a series of organic-inorganic hybrid (OIH) materials [1S,4S-2,5-2.2.1-H2dabch]NaBr3 (2), [1S,4S-2,5-2.2.1-H2dabch]CsCl3·H2O (3) and [1S,4S-2,5-2.2.1-H2dabch]KBr3·H2O (4). The single-crystal X-ray diffraction analysis revealed that the organic-inorganic framework structures comprised of the templating ligand and alkali metal halides (NaBr, CsCl, KBr) displayed dimensions spanning from one-dimensional (1D) to three-dimensional (3D). Moreover, the results of both differential scanning calorimetry (DSC) and dielectric measurements demonstrated that compounds 1-4 displayed reversible, high-temperature phase transitions and noticeable dielectric anomalies. In addition, the temperature-dependent second harmonic generation (SHG) results revealed crystals 1 and 3 can switch from the SHG-ON to the SHG-OFF state, which was proved by the variable-temperature X-ray diffraction. This research aims to streamline the exploration of multifunctional second harmonic generation (SHG) and dielectric materials that have been synthesized using chiral ligands and alkali metals. This will provide researchers with enhanced opportunities to delve further into this specific research domain.

5.
Anal Chem ; 95(34): 12768-12775, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37587155

RESUMO

Herein, a surface-enhanced Raman scattering (SERS) biosensor was constructed by gold nanobipyramid (Au NBP) hotspot aggregation-induced SERS (HAI-SERS) for the ultrasensitive detection of microRNA-221 (miRNA-221). Impressively, compared with single Au NBP, the multiple Au NBPs assembled by tetrahedral DNA nanostructures (TDNs) could increase hotspot aggregation to significantly enhance the SERS signal of Raman molecule methylene blue (MB). Meanwhile, in the aid of Exo-III assisted target cycle amplification and TDNs-induced catalytic hairpin assembly (CHA) amplification, the biosensor could achieve the sensitive detection of miRNA-221 with a linear range of 1 fM-10 nM, and the limit of detection (LOD) was 0.59 fM, which could be used for practical application in MHCC-97L and MCF-7 cell lysates. This work provided a method for hotspot aggregation to enhance SERS for the detection of biomarkers and disease diagnosis.


Assuntos
MicroRNAs , Análise Espectral Raman , Catálise , Ouro , Limite de Detecção
6.
Magn Reson Med ; 90(5): 1979-1989, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37415445

RESUMO

PURPOSE: To develop and evaluate a deep neural network (DeepFittingNet) for T1 /T2 estimation of the most commonly used cardiovascular MR mapping sequences to simplify data processing and improve robustness. THEORY AND METHODS: DeepFittingNet is a 1D neural network composed of a recurrent neural network (RNN) and a fully connected (FCNN) neural network, in which RNN adapts to the different number of input signals from various sequences and FCNN subsequently predicts A, B, and Tx of a three-parameter model. DeepFittingNet was trained using Bloch-equation simulations of MOLLI and saturation-recovery single-shot acquisition (SASHA) T1 mapping sequences, and T2 -prepared balanced SSFP (T2 -prep bSSFP) T2 mapping sequence, with reference values from the curve-fitting method. Several imaging confounders were simulated to improve robustness. The trained DeepFittingNet was tested using phantom and in-vivo signals, and compared to the curve-fitting algorithm. RESULTS: In testing, DeepFittingNet performed T1 /T2 estimation of four sequences with improved robustness in inversion-recovery T1 estimation. The mean bias in phantom T1 and T2 between the curve-fitting and DeepFittingNet was smaller than 30 and 1 ms, respectively. Excellent agreements between both methods was found in the left ventricle and septum T1 /T2 with a mean bias <6 ms. There was no significant difference in the SD of both the left ventricle and septum T1 /T2 between the two methods. CONCLUSION: DeepFittingNet trained with simulations of MOLLI, SASHA, and T2 -prep bSSFP performed T1 /T2 estimation tasks for all these most used sequences. Compared with the curve-fitting algorithm, DeepFittingNet improved the robustness for inversion-recovery T1 estimation and had comparable performance in terms of accuracy and precision.


Assuntos
Coração , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Coração/diagnóstico por imagem , Redes Neurais de Computação , Algoritmos , Ventrículos do Coração , Imagens de Fantasmas , Reprodutibilidade dos Testes
7.
Inorg Chem ; 62(2): 942-949, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36602537

RESUMO

Switchable second harmonic generation (SHG) materials have potential applications in information storage, signal processing, and so on because they can switch between SHG-on and SHG-off states. In this work, we designed and synthesized three organic-inorganic hybrid Rb halide three-dimensional (3D) perovskite materials [1S,4S 2,5-2.2.1-H2dabch]RbX3·0.5H2O (X = Cl, 1; Br, 2; I, 3) based on the chiral 1S,4S-2,5-diazabicyclo[2.2.1]heptane (1S,4S-2,5-2.2.1-dabch). The selection of homochiral organic cations ensures that the compounds 1∼3 crystallize in the noncentrosymmetric and chiral space group P212121, which further leads to reversible SHG responses of the three compounds. Through differential scanning calorimetry (DSC) and dielectric measurements, it revealed that the phase transition point of the compounds 1∼3 increased with RbCl, RbBr, and RbI. This is because the hydrogen interaction H···X between the inorganic framework [RbX3]n and the organic cation [1S,4S-2,5-2.2.1-H2dabch]2+ is increased with the order of I > Br > Cl. This study can provide an effective molecular design strategy for the exploration and construction of temperature-tunable SHG switching materials.

8.
Int J Mol Sci ; 24(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37108431

RESUMO

Leaf senescence reduces the photosynthetic capacity of leaves, thus significantly affecting the growth, development, and yield formation of cotton. Melatonin (MT) is a multipotent substance proven to delay leaf senescence. However, its potential mechanism in delaying leaf senescence induced by abiotic stress remains unclear. This study aimed to explore the effect of MT on delaying drought-induced leaf senescence in cotton seedlings and to clarify its morphological and physiological mechanisms. Drought stress upregulated the leaf senescence marker genes, destroyed the photosystem, and led to excessive accumulation of reactive oxygen species (ROS, e.g., H2O2 and O2-), thus accelerating leaf senescence. However, leaf senescence was significantly delayed when 100 µM MT was sprayed on the leaves of the cotton seedlings. The delay was embodied by the increased chlorophyll content, photosynthetic capacity, and antioxidant enzyme activities, as well as decreased H2O2, O2-, and abscisic acid (ABA) contents by 34.44%, 37.68%, and 29.32%, respectively. MT significantly down-regulated chlorophyll degradation-related genes and senescence marker genes (GhNAC12 and GhWRKY27/71). In addition, MT reduced the chloroplast damage caused by drought-induced leaf senescence and maintained the integrity of the chloroplast lamellae structure under drought stress. The findings of this study collectively suggest that MT can effectively enhance the antioxidant enzyme system, improve photosynthetic efficiency, reduce chlorophyll degradation and ROS accumulation, and inhibit ABA synthesis, thereby delaying drought-induced leaf senescence in cotton.


Assuntos
Melatonina , Melatonina/farmacologia , Melatonina/metabolismo , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Senescência Vegetal , Secas , Peróxido de Hidrogênio/metabolismo , Clorofila/metabolismo , Folhas de Planta/metabolismo , Plântula/metabolismo
9.
Anal Chem ; 94(19): 6967-6975, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35289177

RESUMO

Chemical enhancement with charge transfer (CT) between the adsorbed Raman molecule and the semiconductor mainly contributed to semiconductor surface-enhanced Raman scattering (SERS). In this work, a three-dimensional (3D) WO3 hollow microsphere is first developed as a SERS-active substrate. This 3D WO3 has a smaller band gap and rich surface defects compared with flake WO3. Interestingly, these properties in the WO3 hollow microspheres lead to an increase in charge transfer, which causes a strong CT interaction between the substrate-Raman molecule interfaces, resulting in a large SERS enhancement. The 3D WO3 showed an excellent SERS performance with an enhancement factor (EF) of 1.6 × 106. Finally, a SERS biosensor is constructed based on the above-mentioned semiconductor materials, which can be used for the sensitive detection of miRNA 155 with a limit of detection (LOD) of 0.18 fM by employing a catalytic hairpin assembly (CHA) strategy. This work provides important guidance for semiconductor topography design to improve the SERS performance, supplying a new strategy for biomolecular analysis and disease diagnosis.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Técnicas Biossensoriais/métodos , Limite de Detecção , MicroRNAs/análise , Microesferas , Análise Espectral Raman/métodos
10.
Photosynth Res ; 151(3): 265-277, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34780003

RESUMO

Desert plants evolve different photosynthetic organs to adapt to the extreme environment. We studied the leaf and canopy gas exchange, chlorophyll content, fluorescence parameters, and anatomical structure of different photosynthetic organs (leaf and assimilating stem) on four desert plants (Nitraria sphaerocarpa, Caragana korshinskii, Haloxylon ammodendron, and Calligonum mongolicum). The results showed a higher net photosynthetic rate (PN) in the assimilating stems of H. ammodendron and C. mongolicum, which also had a higher light saturation point and a lower light compensation point than leaves (N. sphaerocarpa and C. korshinskii), suggesting more efficient solar energy utilization in the former. Within each species, canopy apparent photosynthetic rate (CAP) was significantly lower than PN, and the daily average CAP of the assimilating stems was significantly higher than leaves. These findings indicated that the photosynthetic response of desert plants was specific to photosynthetic organs. We concluded that the assimilating stem was a superior adaption for desert plants to survive the arid environments.


Assuntos
Magnoliopsida , Fotossíntese , Clorofila , Fotossíntese/fisiologia , Folhas de Planta/fisiologia , Luz Solar
11.
Chemistry ; 28(71): e202202690, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36168667

RESUMO

The emergence of (CH3 NH3 )PbI3 has brought the development of three-dimensional (3D) organic-inorganic hybrid perovskite (OIHP) structures with ABX3 type to a higher level; however, most 3D frameworks are constructed by corner-sharing of BX6 octahedra. Herein, we substituted the spherical molecule 1,4-diazabicyclo[2.2.2]octane (2.2.2-dabco) with 1,4-diazabicyclo[3.2.2]nonane (1,4-3.2.2-dabcn) as a template to react with RbX (X=Br, I) in the corresponding HX acids under the consideration of reducing the molecular symmetry. Two 3D OIHP compounds [1,4-3.2.2-H2 dabcn]RbI3 ⋅H2 O (1) and [1,4-3.2.2-H2 dabcn]RbBr3 (2) crystallized in non-centrosymmetric point group mm2 before the phase transition point were isolated. Among them, the 3D inorganic framework of 1 is constructed by sharing the corner of [RbI6 ] octahedra, while that of 2 is constructed by sharing the corner and face of [RbBr6 ] octahedra to acquire large cavities to accommodate the organic amine cation [1,4-3.2.2-H2 dabcn]2+ ; this 3D framework type is unprecedented in the OIHPs. As expected, compounds 1 and 2 exhibit reversible phase transition, dielectric and second harmonic generation (SHG) and ferroelectric properties, in which the phase transition temperature of 2 at 374 K is much higher than compound 1 at 280 K.

12.
Int J Mol Sci ; 23(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36293287

RESUMO

Phosphatidyl ethanolamine-binding proteins (PEBPs) are involved in regulating flowering time and various developmental processes. Functions and expression patterns in cultivated peanuts (Arachis hypogaea L.) remain unknown. In this study, 33 PEBP genes in cultivated peanuts were identified and divided into four subgroups: FT, TFL, MFT and FT-like. Gene structure analysis showed that orthologs from A and B genomes in cultivated peanuts had highly similar structures, but some orthologous genes have subgenomic dominance. Gene collinearity and phylogenetic analysis explain that some PEBP genes play key roles in evolution. Cis-element analysis revealed that PEBP genes are mainly regulated by hormones, light signals and stress-related pathways. Multiple PEPB genes had different expression patterns between early and late-flowering genotypes. Further detection of its response to temperature and photoperiod revealed that PEBPs ArahyM2THPA, ArahyEM6VH3, Arahy4GAQ4U, ArahyIZ8FG5, ArahyG6F3P2, ArahyLUT2QN, ArahyDYRS20 and ArahyBBG51B were the key genes controlling the flowering response to different flowering time genotypes, photoperiods and temperature. This study laid the foundation for the functional study of the PEBP gene in cultivated peanuts and the adaptation of peanuts to different environments.


Assuntos
Arachis , Regulação da Expressão Gênica de Plantas , Arachis/genética , Arachis/metabolismo , Filogenia , Flores/metabolismo , Proteínas de Plantas/metabolismo , Genômica , Hormônios/metabolismo , Etanolaminas/metabolismo
13.
Crit Rev Eukaryot Gene Expr ; 31(5): 33-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591388

RESUMO

The microRNA MiR-24-3p suppresses cancer progression by targeting TRIM11. The long noncoding RNA LUADT1 has been reported to promote lung adenocarcinoma proliferation. We found LUADT1 may form base pairing with miR-24-3p. This study aimed to explore the interactions among LUADT1, miR-24-3p, and TRIM11 in mantle cell lymphoma (MCL). Our study recruited 40 MCL patients and 40 healthy volunteers. Tumor tissues were collected from 40 newly diagnosed MCL patients and embedded in paraffin wax. B lymphocytes were isolated from all tissue samples by using CD19+ magnetic beads and DETACHaBEAD CD19. Human MCL cell line Grante-519 and JeKo-1 were transfected with LUADT1 and TRIM11 expression vectors, microRNA mimics or inhibitors. Then, quantitative polymerase chain reaction and Western blot were used to detect the level of relative messenger RNA and protein expression, respectively. Flow cytometry was performed to detect the apoptosis rate. LUADT1 and miR-24-3p were upregulated while TRIM11 was downregulated in MCL both in tissues and cell lines compared with hyperplastic lymphadenitis and peripheral lymphocyte cells. Bioinformatics analysis showed that LUADT1 may bind miR-24-3p, which can target TRIM11. Correlation analysis showed that LUADT1 was not significantly correlated with miR-24-3p. However, it was positively and significantly correlated with TRIM11. In MCL cells, LUADT1 overexpression led to upregulated TRIM11, whereas miR-24-3p overexpression led to downregulated TRIM11. Cell apoptosis analysis showed that LU-ADT1, miR-24-3p inhibitor and TRIM11 overexpression led to decreased apoptotic rate of MCL cells, whereas miR-24-3p overexpression led to an increased apoptotic rate of MCL cells. In addition, miR-24-3p overexpression attenuated the effects of LUADT1 overexpression. Therefore, LUADT1 was upregulated in MCL and could modulate TRIM11 by sponging miR-24-3p to inhibit cancer cell apoptosis.


Assuntos
Apoptose , Linfócitos B/metabolismo , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética
14.
Nutr Cancer ; 73(11-12): 2188-2200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33225744

RESUMO

Lung cancer is one of the common types of malignant disorders and the most prevalent cause of cancer-related mortality in the world. Although a wide range of approaches has been examined, strategies in prevention and treatment of lung cancer are still inadequate. Studies show that Vitamin D (VitD) is involved in various biological pathways and has been associated with the etiopathogenesis of several diseases, like cancers. In Vitro and In Vivo experiments have disclosed that VitD plays immunomodulatory and anti-tumor functions. Several lines of evidence have indicated that VitD is involved in the inflammatory settings of the lung. Epidemiological studies have reported that sufficient levels of VitD might be critical in the prevention of lung cancer. Polymorphisms in the genes encoding the different molecules involved in the signaling of VitD might affect the lung cancer risk as well as the quality and quantity of responses to different treatments. In this review article, we intended to clarify the implications of VitD in the normal biology and physiology of the lung and discuss diverse line of evidence about the possible role of VitD in the prevention or treatment of lung cancer.


Assuntos
Neoplasias Pulmonares , Deficiência de Vitamina D , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/prevenção & controle , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas
15.
Biogerontology ; 21(5): 495-516, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32285331

RESUMO

The vascular endothelium is a protective barrier between the bloodstream and the vasculature that may be disrupted by different factors such as the presence of diseased states. Diseases like diabetes and obesity pose a great risk toward endothelial cell inflammation and oxidative stress, leading to endothelial cell dysfunction and thereby cardiovascular complications such as atherosclerosis. Sirtuins are NAD+-dependent histone deacetylases that are implicated in the pathophysiology of cardiovascular diseases, and they have been identified to be important regulators of endothelial cell function. A handful of recent studies suggest that disbalance in the regulation of endothelial sirtuins, mainly sirtuin 1 (SIRT1), contributes to endothelial cell dysfunction. Herein, we summarize how SIRT1 and other sirtuins may contribute to endothelial cell function and how presence of diseased conditions may alter their expressions to cause endothelial dysfunction. Moreover, we discuss how the beneficial effects of exercise on the endothelium are dependent on SIRT1. These mainly include regulation of signaling pathways related to endothelial nitric oxide synthase phosphorylation and nitric oxide production, mitochondrial biogenesis and mitochondria-mediated apoptotic pathways, oxidative stress and inflammatory pathways. Sirtuins as modulators of the adverse conditions in the endothelium hold a promising therapeutic potential for health conditions related to endothelial dysfunction and vascular ageing.


Assuntos
Envelhecimento , Células Endoteliais/patologia , Endotélio Vascular/fisiopatologia , Sirtuínas , Doenças Vasculares , Humanos , Inflamação , Estresse Oxidativo , Transdução de Sinais , Sirtuína 1 , Sirtuínas/fisiologia
16.
Pharmacology ; 105(5-6): 339-348, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31722363

RESUMO

Depression is a progressive and chronic syndrome and commonly related to several neuropsychiatric comorbidities, of which depression is the most studied. Population-based studies have suggested a positive role of statins in ameliorating depression risk. However, the role of statins in the treatment of diabetes-related depression has not been well examined. Herein, we investigated the effects of lovastatin (LOV) on depressive phenotypes in streptozotocin-induced diabetic mice. The data suggested that the treatment of LOV at 10 or 20 mg/kg for 3 weeks markedly prevented diabetes-associated depressive behaviors reflected by better performance in the sucrose preference test, tail suspension test, and novelty-suppressed feeding test. The study further showed that these treatments improved the hippocampal neurogenesis as evidenced by increased bromodeoxyuridine-positive cells in the dentate gyrus with higher expression of mature brain-derived neurotrophic factor and increased phosphorylation of cAMP-response element-binding protein. As expected, diabetic mice treated with LOV showed significant improvement of hyperlipidemia rather than hyperglycemia. These results suggest that LOV may be employed as a drug for the treatment of diabetes-related depression.


Assuntos
Depressão/prevenção & controle , Diabetes Mellitus Experimental/complicações , Hipocampo/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lovastatina/uso terapêutico , Neurogênese/efeitos dos fármacos , Animais , Antidepressivos , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Depressão/etiologia , Diabetes Mellitus Experimental/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Psicológico
17.
Mol Cell Biochem ; 450(1-2): 167-174, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29926321

RESUMO

The basic helix-loop-helix (bHLH) superfamily of transcription factors have been implicated in a wide range of cellular functions such as proliferation, differentiation, tumorigenesis, and circadian rhythms. In a previous siRNA-based screen, bHLH family member e41 (BHLHE41) had been identified as a putative regulator of neuronal differentiation; however, its function remains largely elusive. To this end, using the CRISPR-Cas9 system, we established an isogenic Neuro2a (N2a) cell line with biallelic targeting of Bhlhe41 gene (Bhlhe41-/-). In undifferentiated N2a cells, complete knockout of Bhlhe41 resulted in marked proliferation inhibition, together with accumulation of apoptotic cells. Furthermore, retinoic acid (RA)-induced neurite outgrowth and expression of neuronal markers are significantly weakened in Bhlhe41-/- cells. We also showed that the activity of ERK1/2 signaling, a key regulator of neuronal differentiation, is likewise impaired in knockout cells. Together, these results suggest that Bhlhe41 plays critical roles in regulating cell death and neurite outgrowth in N2a cells.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular , Proliferação de Células , Sistema de Sinalização das MAP Quinases , Neuritos/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Sistemas CRISPR-Cas , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular , Deleção de Genes , Camundongos , Tretinoína/farmacologia
18.
Plant J ; 90(5): 839-855, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28370754

RESUMO

In natural or agricultural environments, plants are constantly exposed to a wide range of biotic and abiotic stresses. Given the forecasted global climate changes, plants will cope with heat waves, drought periods and pathogens at the same time or consecutively. Heat and drought cause opposing physiological responses, while pathogens may or may not profit from climate changes depending on their lifestyle. Several studies have been conducted to find stress-specific signatures or stress-independent commonalities. Previously this has been done by comparing different single stress treatments. This approach has been proven difficult since most studies, comparing single and combined stress conditions, have come to the conclusion that each stress treatment results in specific transcriptional changes. Although transcriptional changes at the level of individual genes are highly variable and stress-specific, central metabolic and signaling responses seem to be common, often leading to an overall reduced plant growth. Understanding how specific transcriptional changes are linked to stress adaptations and identifying central hubs controlling this interaction will be the challenge for the coming years. In this review, we will summarize current knowledge on plant responses to different individual and combined stresses and try to find a common thread potentially underlying these responses. We will begin with a brief summary of known physiological, metabolic, transcriptional and hormonal responses to individual stresses, elucidate potential commonalities and conflicts and finally we will describe results obtained during combined stress experiments. Here we will concentrate on simultaneous application of stress conditions but we will also touch consequences of sequential stress treatments.


Assuntos
Regulação da Expressão Gênica de Plantas/fisiologia , Desenvolvimento Vegetal/fisiologia , Mudança Climática , Secas , Regulação da Expressão Gênica de Plantas/genética , Temperatura Alta , Desenvolvimento Vegetal/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
19.
Cell Physiol Biochem ; 51(2): 681-691, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30463061

RESUMO

BACKGROUND/AIMS: We aimed to explore the protective role of curcumin (Cur) in a cell model of Parkinson's disease (PD) and its underlying mechanism. METHODS: In this study, genes concerned with PD-related keywords were screened within DiGSeE database. The association network between Cur and selected genes was downloaded from STITCH, with the interactions analyzed by STRING. We built a mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cell model of PD. Cell morphology was observed under an electron microscope. MTT assay was applied to detect cell proliferation rate. Western blot assay was conducted to determine the level of apoptotic markers, including cleaved caspase 3, Bcl-2-associated X protein (Bax) and B-cell lymphoma-extra-large (Bcl-xl). Tyrosine hydroxylase (TH), dopamine transporter (DAT) protein levels and dopamine (DA) concentration were identified as dopaminergic neuron markers and measured by western blotting or Enzyme-linked immunosorbent assay (ELISA). RESULTS: Cur rescued the toxicity effects of MPP+ on SH-SY5Y cells, by controlling morphological change, promoting cell proliferation and inhibiting apoptosis. Of all PD-related genes, HSP90 played an important role in Cur-gene network. HSP90 protein level was elevated by MPP+, whereas Cur could reverse this effect. Silencing of HSP90 significantly attenuated the curative effect introduced by Cur, while HSP90 overexpression enhanced the impact of Cur on PD. CONCLUSION: Cur can effectively inhibit the toxic effect of MPP+ on SH-SY5Y cells and significantly reduce the adverse effects of MPP+ on dopaminergic neurons via up-regulation of HSP90.


Assuntos
Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Proteínas de Choque Térmico HSP90/metabolismo , 1-Metil-4-fenilpiridínio/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dopamina/análise , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Redes Reguladoras de Genes , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/genética , Humanos , Modelos Biológicos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
20.
Chemistry ; 20(17): 4885-90, 2014 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-24648263

RESUMO

The syntheses and structures of two new Zn(II) complexes, a 2D graphite-like layer {[Zn(PIA)H2 O]⋅H2 O}n (1) and an independent 1D single-walled metal-organic nanotube (SWMONT) {[Zn2 (PIA)2 (bpy)2 ]⋅2.5 H2 O⋅DMA}n (2), have been reported based on a "Y"-shaped 5-(pyridine-4-yl)isophthalic acid ligand (H2 PIA). Interestingly, the 2D graphite-like layer in 1 can transform into the independent 1D SWMONT in 2 with addition of 2,2'-bipyridine (bpy), which represents the first successfully experimental example of an independent 1D metal-organic nanotube generated from a 2D layer by a "rolling-up" mechanism.

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