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1.
J Am Chem Soc ; 146(17): 12053-12062, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38622809

RESUMO

Three-component diene carboaminations offer a potent means to access synthetically valuable allylic amines with rapid molecular complexity escalation. The existing literature primarily discloses racemic examples, necessitating the use of halides/pseudohalides as substrates. This paper introduces a photoinduced Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes, leveraging aliphatic C-H bonds for rapid synthesis. The reaction employs 10 mol % of chiral palladium catalyst and an excess aryl bromide as the HAT reagent. This approach yields diverse chiral allylamines with moderate to excellent enantioselectivities. Notably, it stands as the first instance of an asymmetric three-component diene carboamination reaction, directly utilizing abundant C(sp3)-H bearing partners, such as toluene-type substrates, ethers, amines, esters, and ketones. The protocol exhibits versatility across amines, encompassing aliphatic, aromatic, primary, and secondary derivatives. This method could serve as a versatile platform for stereoselective incorporation of various nucleophiles, dienes, and C(sp3)-H bearing partners.

2.
Cytokine ; 182: 156724, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39106574

RESUMO

Obesity, cardiovascular diseases (CVD), and nonalcoholic fatty liver disease (NAFLD) pose significant worldwide health challenges, characterized by complex interplay among inflammatory pathways that underlie their development. In this review, we examine the contribution of inflammation and associated signaling molecules to the pathogenesis of these conditions, while also emphasizing the significant participation of non-coding RNAs (ncRNAs) in modulating inflammatory pathways. In the context of obesity, aberrant expression patterns of inflammatory-associated miRNAs play a contributory role in adipose tissue inflammation and insulin resistance, thereby exacerbating disturbances in metabolic homeostasis. Similarly, in CVD, dysregulated miRNA expression alters inflammatory reactions, disrupts endothelial function, and induces cardiac remodeling, thereby impacting the advancement of the disease. Moreover, in the context of NAFLD, inflammatory-associated miRNAs are implicated in mediating hepatic inflammation, lipid deposition, and fibrosis, underscoring their candidacy as promising therapeutic targets. Additionally, the competing endogenous RNA (ceRNA) network has emerged as a novel regulatory mechanism in the etiology of CVD, obesity, and NAFLD, wherein ncRNAs assume pivotal roles in facilitating communication across diverse molecular pathways. Moreover, in the concluding section, we underscored the potential efficacy of directing interventions towards inflammatory-related miRNAs utilizing herbal remedies and therapies based on exosome delivery systems as a promising strategy for ameliorating pathologies associated with inflammation in obesity, CVD, and NAFLD.


Assuntos
Doenças Cardiovasculares , Inflamação , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Obesidade , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Inflamação/genética , Inflamação/metabolismo , Obesidade/genética , Obesidade/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Animais
3.
Org Biomol Chem ; 21(36): 7305-7310, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37668247

RESUMO

A highly enantio- and diastereoselective approach has been developed for the synthesis of chiral phosphono dihydropyranones. This approach is enabled by Pd/chiral isothiourea relay catalysis under mild reaction conditions, starting from readily available benzyl bromides, CO, and α-ketophosphonates. The cascade reaction involves the generation of a ketene intermediate from Pd-catalyzed carbonylation of benzyl bromide and subsequent chiral Lewis base catalyzed formal [4 + 2] reaction. Phosphono lactone products can also be transformed to chiral 1,5-diester products in good yield and high stereoselectivity.

4.
Acc Chem Res ; 54(23): 4294-4304, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34719918

RESUMO

As renewable energy sources are either intermittent in nature or remote in location, developing cost-effective, sustainable, modular systems and technologies to store and transport renewables at an industrial scale is imperative. Storing cheap renewable electricity into chemical bonds (i.e., chemical energy storage) could be a transformative opportunity for reliable and resilient grid energy storage. This approach enables renewables to be stored and shipped similarly to fossil fuels. Currently, the chemical industry primarily consumes fossil feedstock as an energy source, which has been the standard for over a century. A paradigm shift is required to move toward a more sustainable route for chemical synthesis by electrifying and decarbonizing the modern chemical industry. As renewable electricity costs decrease, (photo)electrosynthesis is gaining interest for synthesizing high-value and high-energy fuels and molecules in a clean, sustainable, and decentralized manner.The nitrogen cycle is one of the Earth's most critical biogeochemical cycles since nitrogen is a vital element for all living organisms. Artificial nitrogen fixation via a (photo)electrochemical system powered by renewables provides an alternative route to resource- and carbon-intensive thermochemical processes. (Photo)electrochemical nitrogen fixation at a large scale necessitates the discovery of active, selective, and stable heterogeneous (photo)electrocatalysts. In addition, the use of advanced in situ and operando spectroscopic techniques is needed to pinpoint the underlying reaction mechanisms. The selectivity of nitrogen (N2) molecules on the catalyst surface and suppressing thermodynamically favorable side reactions (e.g., hydrogen evolution reaction) are the main bottlenecks in improving the rate of (photo)electrochemical nitrogen fixation in aqueous solutions. The rational design of electrode, electrolyte, and reactors is required to weaken the strong nitrogen-nitrogen triple bond (N≡N) at or near ambient conditions. This Account covers our group's recent advances in synthesizing shape-controlled hybrid plasmonic nanoparticles, including plasmonic-semiconductor and plasmonic-transition metal nanostructures with increased surface areas. The nanocatalysts' selectivity and activity toward nitrogen conversion are benchmarked in liquid- and gas-phase electrochemical systems. We leverage operando vibrational-type spectroscopy (i.e., surface-enhanced Raman spectroscopy (SERS)) to identify intermediate species relevant to nitrogen fixation at the electrode-electrolyte interface to gain mechanistic insights into reaction mechanisms, leading to the discovery of more efficient catalysts. Operando SERS revealed that the nitrogen reduction reaction (NRR) to ammonia on hybrid plasmonic-transition metal nanoparticle surfaces (e.g., Pd-Ag) occurs through an associative mechanism. In the NRR process, hydrazine (N2H4) is consumed as an intermediate species. A femtosecond pulsed laser is used to synthesize hybrid plasmonic photocatalysts with homogeneously distributed Pd atoms on a Au nanorod surface, resulting in enhanced optoelectronic and catalytic properties. The overarching goal is to develop modular photoelectrochemical systems for long-duration renewable energy storage. In the context of nitrogen fixation, we aim to propose strategies to manage the nitrogen cycle through the interconversion of N2 and active nitrogen-containing compounds (e.g., NH3, NOx), enabling a circular nitrogen economy with sustainable and positive social and economic outcomes. The versatile approaches presented in this Account can inform future opportunities in (photo)electrochemical energy conversion systems and solar fuel-based applications.

5.
Nanomedicine ; 42: 102544, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35192939

RESUMO

Although chemotherapy has been known as a powerful medication for cancer treatment over the years, there is an important necessity for designing a novel targeted drug delivery system to overcome the drawbacks of this conventional method including undesired side effects on normal cells and drug resistance. The structural differences between the surface of cancerous and normal cells allow to design and engineer targeted drug delivery systems for cancer treatment. Integrins as one of the cell surface receptors over-expressed in cancer cells could potentially be suitable candidates for targeting cancer cells. In the present study, the novel nano-carriers based on designed MiRGD peptides and graphene quantum dots (GQDs) have been used for targeted delivery of doxorubicin (Dox) and curcumin (Cur) as hydrophilic and hydrophobic drug models, respectively. The prepared nano-composites were characterized by UV-vis and photoluminescence (PL) spectroscopies, Zeta-Sizer and transmission electron microscopy (TEM). Altogether, the results of cellular uptake and fluorimetric assays performed in HUVEC and HFF cells as models of αv integrin-over-expressed cancer and normal cells, respectively, besides in-vivo study on breast cancer bearing BALB/c mice, demonstrated that the prepared nano-composites can be considered as suitable multifunctional theranostic peptideticles for targeted drug delivery and tracking.


Assuntos
Neoplasias da Mama , Curcumina , Grafite , Pontos Quânticos , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Curcumina/farmacologia , Curcumina/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Grafite/química , Humanos , Camundongos , Peptídeos/uso terapêutico , Medicina de Precisão , Pontos Quânticos/química , Nanomedicina Teranóstica
6.
Proc Natl Acad Sci U S A ; 116(39): 19299-19304, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31488713

RESUMO

We present a systematic study of the effect of higher-multipolar order plasmon modes on the spectral response and plasmonic coupling of silver nanoparticle dimers at nanojunction separation and introduce a coupling mechanism. The most prominent plasmonic band within the extinction spectra of coupled resonators is the dipolar coupling band. A detailed calculation of the plasmonic coupling between equivalent particles suggests that the coupling is not limited to the overlap between the main bands of individual particles but can also be affected by the contribution of the higher-order modes in the multipolar region. This requires an appropriate description of the mechanism that goes beyond the general coupling phenomenon introduced as the plasmonic ruler equation in 2007. In the present work, we found that the plasmonic coupling of nearby Ag nanocubes does not only depend on the plasmonic properties of the main band. The results suggest the decay length of the higher-order plasmon mode is more sensitive to changes in the magnitude of the interparticle axis and is a function of the gap size. For cubic particles, the contribution of the higher-order modes becomes significant due to the high density of oscillating dipoles localized on the corners. This gives rise to changes in the decay length of the plasmonic ruler equation. For spherical particles, as the size of the particle increases (i.e., ≥80 nm), the number of dipoles increases, which results in higher dipole-multipole interactions. This exhibits a strong impact on the plasmonic coupling, even at long separation distances (20 nm).

7.
Nano Lett ; 21(3): 1238-1245, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33481600

RESUMO

Efficient hybrid plasmonic-photonic metasurfaces that simultaneously take advantage of the potential of both pure metallic and all-dielectric nanoantennas are identified as an emerging technology in flat optics. Nevertheless, postfabrication tunable hybrid metasurfaces are still elusive. Here, we present a reconfigurable hybrid metasurface platform by incorporating the phase-change material Ge2Sb2Te5 (GST) into metal-dielectric meta-atoms for active and nonvolatile tuning of properties of light. We systematically design a reduced-dimension meta-atom, which selectively controls the hybrid plasmonic-photonic resonances of the metasurface via the dynamic change of optical constants of GST without compromising the scattering efficiency. As a proof-of-concept, we experimentally demonstrate two tunable metasurfaces that control the amplitude (with relative modulation depth as high as ≈80%) or phase (with tunability >230°) of incident light promising for high-contrast optical switching and efficient anomalous to specular beam deflection, respectively. Our findings further substantiate dynamic hybrid metasurfaces as compelling candidates for next-generation reprogrammable meta-optics.

8.
Genomics ; 112(3): 2615-2622, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32068121

RESUMO

Lung cancer is a leading cause of cancer-related death in the world. Therefore, identifying the genes and molecular pathways involved in lung development and tumorigenesis can help us improve the therapeutic strategies of lung cancer. Accumulating evidence confirms that long noncoding RNAs, as a novel layer of regulatory RNA molecules, play an important role in various aspects of the cells. Here, using available high throughput gene expression data, we identified an lncRNA (HSPC324) with high expression level in lung tissue that is distinctly expressed in lung tumor tissues relative to normal. Using GO enrichment and KEGG pathway analyses, we further analyzed the functions and pathways involving the HSPC324-correlated genes. Ectopic expression of lncRNA HSPC324 significantly inhibited proliferation, cell cycle and migration; on the other hand, increased apoptosis and ROS production in lung adenocarcinoma cells. Overall, this study introduces HSPC324 as a new player in the development of lung cancer.


Assuntos
Neoplasias Pulmonares/genética , Pulmão/crescimento & desenvolvimento , RNA Longo não Codificante/fisiologia , Apoptose , Carcinogênese/genética , Ciclo Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio/metabolismo
9.
Anal Biochem ; 598: 113645, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105739

RESUMO

New lanthanide complexes (1-3) of the general formulae [Ln(L)(NO3)(H2O)] have been synthesized by reaction of Ln(NO3)3 {Ln = La (1), Sm (2) and Yb (3)} with 2,2'-(((1E,1'E)-thiophene-2,5-diylbis(methaneylylidene))bis(azaneylylidene))diphenol (H2L). Based on elemental analysis, spectroscopic studies (UV-Vis., FT-IR, ESI-MS, 1H/13C NMR), molar conductance and thermogravimetric analysis, the Schiff base ligand was suggested to coordinate Ln(III) ions through the azomethine nitrogens, deprotonated hydroxyl groups, and thiophene sulphur atom. The interaction of the synthetic compounds with CT-DNA has been studied by the electronic spectroscopy, fluorometric competition studies with ethidium bromide and DNA viscosity measurements. Furthermore, due to the ligand and its Ln(III) complexes exhibit good DNA binding affinity, it is considered worthwhile to investigate their antioxidant activity. The data have shown that, the complexes are more effective inhibitors towards reactive oxygen species (ROS), such as superoxide anion and hydroxyl radical. The activity of test compounds in ascending order (1) > (2) > (3) > H2L in terms of IC50 value. The anticancer activities of the complexes have also been studied towards human colon carcinoma cancer (HCT-116) and human breast cancer (MCF-7) cell lines.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Complexos de Coordenação/farmacologia , Elementos da Série dos Lantanídeos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Aspergillus flavus/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , DNA/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Elementos da Série dos Lantanídeos/química , Células MCF-7 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Rhizoctonia/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Superóxidos/antagonistas & inibidores , Viscosidade
10.
Proc Natl Acad Sci U S A ; 114(28): E5655-E5663, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28652358

RESUMO

Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are not effective. Recently, gold nanoparticles (AuNPs) were discovered to inhibit cancer cell migration and prevent metastasis. Rationally designed AuNPs could greatly benefit their antimigration property, but the molecular mechanisms need to be explored. Cytoskeletons are cell structural proteins that closely relate to migration, and surface receptor integrins play critical roles in controlling the organization of cytoskeletons. Herein, we developed a strategy to inhibit cancer cell migration by targeting integrins, using Arg-Gly-Asp (RGD) peptide-functionalized gold nanorods. To enhance the effect, AuNRs were further activated with 808-nm near-infrared (NIR) light to generate heat for photothermal therapy (PPTT), where the temperature was adjusted not to affect the cell viability/proliferation. Our results demonstrate changes in cell morphology, observed as cytoskeleton protrusions-i.e., lamellipodia and filopodia-were reduced after treatment. The Western blot analysis indicates the downstream effectors of integrin were attracted toward the antimigration direction. Proteomics results indicated broad perturbations in four signaling pathways, Rho GTPases, actin, microtubule, and kinases-related pathways, which are the downstream regulators of integrins. Due to the dominant role of integrins in controlling cytoskeleton, focal adhesion, actomyosin contraction, and actin and microtubule assembly have been disrupted by targeting integrins. PPTT further enhanced the remodeling of cytoskeletal proteins and decreased migration. In summary, the ability of targeting AuNRs to cancer cell integrins and the introduction of PPTT stimulated broad regulation on the cytoskeleton, which provides the evidence for a potential medical application for controlling cancer metastasis.


Assuntos
Citoesqueleto/metabolismo , Ouro/química , Integrinas/metabolismo , Nanotubos/química , Neoplasias/patologia , Neoplasias/terapia , Fototerapia/métodos , Actomiosina/metabolismo , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Proteínas do Citoesqueleto , Dissulfetos , Humanos , Hipertermia Induzida , Neoplasias Bucais/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/metabolismo , Proteômica
11.
Proc Natl Acad Sci U S A ; 114(15): E3110-E3118, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28356516

RESUMO

Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2.5 nM) of AuNRs and the PPTT laser power (2 W/cm2) to achieve maximal induction of apoptosis. Second, we studied the potential mechanism of action of AuNRs-PPTT using quantitative proteomic analysis in mouse tumor tissues. Several death pathways were identified, mainly involving apoptosis and cell death by releasing neutrophil extracellular traps (NETs) (NETosis), which were more obvious upon PPTT using RF-conjugated AuNRs (AuNRs@RF) than with polyethylene glycol thiol-conjugated AuNRs. Cytochrome c and p53-related apoptosis mechanisms were identified as contributing to the enhanced effect of PPTT with AuNRs@RF. Furthermore, Pin1 and IL18-related signaling contributed to the observed perturbation of the NETosis pathway by PPTT with AuNRs@RF. Third, we report a 15-month toxicity study that showed no long-term toxicity of AuNRs in vivo. Together, these data demonstrate that our AuNRs-PPTT platform is effective and safe for cancer therapy in mouse models. These findings provide a strong framework for the translation of PPTT to the clinic.


Assuntos
Carcinoma de Células Escamosas/terapia , Ouro/farmacologia , Neoplasias de Cabeça e Pescoço/terapia , Hipertermia Induzida , Lasers , Nanotubos/química , Fototerapia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Feminino , Ouro/química , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteômica , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Nano Lett ; 19(3): 2037-2043, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30803236

RESUMO

While Li-ion battery cathode-electrolyte interfaces (CEIs) have been extensively investigated in recent decades, accurately identifying the chemical nature and tracking the dynamics of the CEIs during electrochemical cycling still remain a grand challenge. Here we report our findings in the investigation into the dynamic evolution of the interface between a LiNi0.33Co0.33Mn0.33O2 (LNMC) cathode and an ethylene carbonate/dimethyl carbonate (EC/DMC)-based electrolyte using surface-enhanced Raman spectroscopy (SERS) performed on a model cell under typical battery operating conditions. In particular, the strong SERS activity provided by a monolayer of Au nanocubes deposited on a model LNMC electrode (additive-free) enables quasi-quantitative assessment of the CEI evolution during cycling, proving information vital to revealing the dynamics of the species adsorbed on the LNMC surface as a function of cell potential. Furthermore, our theoretical calculation, which is based on the interaction between a model interface-bound molecule and a model LNMC surface, agrees with our experimental observation. The carefully designed operando SERS platform has demonstrated high sensitivity, good surface specificity, and excellent compatibility with extensive electrochemical measurements; it is also applicable to fundamental studies of dynamic interfaces in other electrochemical energy storage and conversion systems.

13.
J Cell Physiol ; 234(8): 13773-13780, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30666656

RESUMO

The critical role of Notch signaling has been shown in the pathogenesis of some neurological disorders including schizophrenia, epilepsy and Alzheimer's disease. This study was aimed to evaluate the role of Notch 1 receptor in epileptogenesis as well as seizure characteristics. The animals were divided into three groups of sham, early stage and end stage. In sham group: Normal saline was injected intraperitoneally (ip) in the same as protocol of pentylenetetrazol (PTZ) injection. PTZ was injected (ip) every 48 hr over a period of 1 week in the group of early stage and over a period of 4 weeks in the end stage. The gene expression as well as distribution of Notch 1 receptor was assessed in the parietal cortex and hippocampus. In addition, the effect of agonist or antagonist of Notch 1 receptor was assessed on the epileptic discharges induced by PTZ injection. The gene expression of Notch 1 decreased in the hippocampus significantly in the end-stage group compared with sham, and early groups. Furthermore, distribution of Notch 1 receptor increased in the somatosensory cortex and decreased in the CA1 hippocampal area in the end-stage group. Intraventricular microinjection of Notch 1 agonist significantly increased the amplitude as well as frequency of spikes and decreased the latency of first epileptic discharges. Our findings illustrate the critical role of Notch signalling as a potential pathway in the epileptogenesis during development of chronic seizures.


Assuntos
Encéfalo/metabolismo , Receptor Notch1/metabolismo , Convulsões/metabolismo , Animais , Doença Crônica , Masculino , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia
14.
J Cell Biochem ; 120(11): 19172-19185, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31271232

RESUMO

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer among smokers, nonsmokers, women, and young individuals. Tobacco smoking and different stages of the NSCLC have important roles in cancer evolution and require different treatments. Existence of poorly effective therapeutic options for the NSCLC brings special attention to targeted therapies by considering genetic alterations. In this study, we used RNA-Seq data to compare expression levels of RefSeq genes and to find some genes with similar expression levels. We utilized the "Weighted Gene Co-expression Network Analysis" method for three different datasets to create coexpressed genetic modules having relations with the smoking status and different stages of the NSCLC. Our results indicate seven important genetic modules having important associations with the smoking status and cancer stages. Based on investigated genetic modules and their biological explanation, we then identified 13 newly candidate genes and 7 novel transcription factors in association with the NSCLC, the smoking status, and cancer stages. We then examined those results using other datasets and explained our results biologically to illustrate some important genes in relation with the smoking status and metastatic stage of the NSCLC that can bring some crucial information about cancer evolution. Our genetic findings also can be used as some therapeutic targets for different clinical conditions of the NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Pulmonares , Transdução de Sinais/genética , Fumar , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Fumar/genética , Fumar/metabolismo , Fumar/patologia
15.
J Cell Biochem ; 120(6): 10248-10272, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30592328

RESUMO

The phosphatidylinositol 3-kinases (PI3K)/Akt signaling pathway is one of the well-characterized and most important signaling pathways activated in response to DNA damage. This review discusses the most recent discoveries on the involvement of PI3K/Akt signaling pathway in cancer development, as well as stimulation of some important signaling networks involved in the maintenance of cellular homeostasis upon DNA damage, with an exploration of how PI3K/Akt signaling pathway contributes to the regulation of modulators and effectors underlying DNA damage response, the intricate, protein-based signal transduction network, which decides between cell cycle arrest, DNA repair, and apoptosis, the elimination of irreparably damaged cells to maintain homeostasis. The review continues by looking at the interplay between cell cycle checkpoints, checking the repair of damage inflicted to the DNA before entering DNA replication to facilitate DNA synthesis, and PI3K/Akt signaling pathway. We then investigate the challenges the cells overcome to ameliorate damages induced by oxidative activities, for example, the recruitment of many pathways and factors to maintain integrity and hemostasis. Finally, the review provides a discussion of how cells use the PI3K/Akt signaling pathway to regulate the balance between these networks.


Assuntos
Pontos de Checagem do Ciclo Celular , Dano ao DNA , Neoplasias/patologia , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Apoptose , Reparo do DNA , Humanos , Neoplasias/metabolismo
16.
J Cell Biochem ; 120(5): 8280-8290, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30485511

RESUMO

Non-small-lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC could pave the way for effective therapies. Analysis of molecular genetic biomarkers in biological fluids has been proposed as a useful tool for cancer diagnosis. Here, we aimed to develop a panel of noncoding RNAs (ncRNAs) in sputum for NSCLC early detection. Expression of 11 ncRNAs were analyzed by real-time polymerase chain reaction in sputum samples of 30 NSCLC patients and 30 sex- and age-matched cancer-free controls. Stability of endogenous microRNAs (miRNAs) in sputum was evaluated after 3 and 6 days at 4°C, 6 months, and 1 year at -80°C. Nine ncRNAs showed significant differences of their expression in sputum between NSCLC patients and controls. A logistic regression model with the best prediction was built based on miR-145, miR-126, and miR-7. The composite of the three miRNAs produced 90% sensitivity and specificity in distinguishing NSCLC patients from the controls. Results indicate that miRNAs could be useful biomarkers based on their stability under various storage conditions and maintain differential changes between cancer and control groups. Moreover, measurement of miRNAs in sputum could be a noninvasive approach for detection of lung cancer.

17.
Neurobiol Dis ; 124: 416-427, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30590180

RESUMO

Neuropathological findings in the amygdala obtained from patients with mesial temporal lobe epilepsy (MTLE) indicate varying degrees of histopathological alterations, such as neuronal loss and gliosis. The mechanisms underlying cellular damage in the amygdala of patients with MTLE have not been fully elucidated. In the present study, we assess cellular damage, determine the receptor expression of major inhibitory and excitatory neurotransmitters, and evaluate the correlation between the expression of various receptors and cell damage in the basolateral complex and the centromedial areas in the amygdala specimens resected during brain surgery on 30 patients with medically intractable MTLE. Our data reveal an increased rate of cell damage and apoptosis as well as decreased expression levels of several GABAergic receptor subunits (GABAARα1, GABAARß3, and GABABR1) and GAD65 in the amygdalae obtained during epilepsy surgery compared to autopsy specimens. Analyses of the expression of glutamate excitatory receptor subunits (NR1, NR2B, mGluR1α, GluR1, and GluR2) reveal no significant differences between the epileptic amygdalae and autopsy control tissues. Furthermore, the increased occurrence of apoptotic cells in the amygdala is negatively correlated with the reduced expression of the studied GABAergic receptor subunits and GAD65 but is not correlated with the expression of excitatory receptors. The present data point to the importance of GABAergic neurotransmission in seizure-induced cell injury in the amygdala of patients with MTLE and suggest several GABA receptor subunits as potential druggable target structures to control epilepsy and its comorbid disorders, such as anxiety.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Receptores de GABA/biossíntese , Adolescente , Adulto , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Apoptose/fisiologia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transmissão Sináptica/fisiologia , Adulto Jovem
18.
Anal Chem ; 91(22): 14261-14267, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31647626

RESUMO

Due to the considerable amount of applications of gold nanoparticles (AuNPs) in biological systems, there is a great need for an improved methodology to quantitatively measure the uptake of AuNPs in cells. Flow cytometry has the ability to measure intracellular AuNPs by collecting the light scattering from a large population of live cells through efficient single cell analysis. Traditionally, the side scattering setting of the flow cytometer, which is associated with a 488 nm excitation laser (SSC channel), is used to detect nanoparticle uptake. This method is limited as AuNPs do not have the optimized response when excited with this laser. Here, we reported that the use of more red-shifted excitation lasers will greatly enhance the optical signal needed for the flow cytometry-based detection of AuNSs (26 nm in diameter) and AuNRs (67 nm × 33 nm, length × width) uptake in triple negative breast cancer cells (MDA-MB-231).


Assuntos
Citometria de Fluxo/instrumentação , Ouro/farmacocinética , Nanopartículas Metálicas/análise , Transporte Biológico , Linhagem Celular Tumoral , Desenho de Equipamento , Feminino , Ouro/análise , Humanos , Lasers , Tamanho da Partícula , Neoplasias de Mama Triplo Negativas/metabolismo
19.
Mol Biol Rep ; 46(2): 2059-2066, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30725348

RESUMO

Derived from rosaceous plant seed, amygdalin belongs to aromatic cyanogenic glycoside group, and its anticancer effects have been supported by mounting evidence. In this study, we objected to investigate amygdalin effect on two antiapoptotic genes (Survivin, XIAP) and two lncRNAs (GAS5, MALAT1) in human cancer cells (A549, MCF7, AGS). Employing RT-qPCR analysis, we compared the mRNA levels of the genes related to apoptosis in A549, MCF7, and AGS cancer cells between amygdalin-treated (24, 48 and 72 h) and un-treated groups. RNA was extracted from both cell groups and then cDNAs were synthesized. The changes in the gene expression levels were specified using ΔΔCt method. RT-qPCR analysis has revealed that the expression of Survivin, XIAP, GAS5 and MALAT1 in amygdala-treated cancer cells were significantly different, compared to the un-treated cells. However, these expressions were different depending on the treatment time. According to the results, amygdalin significantly inhibited the expression level of Survivin, and XIAP genes in treated via untreated group. Our findings suggest that amygdalin might have an anticancer effect due to the various gene expressions in A549, MCF7, and AGS human cancer cells, showing it's potential as a natural therapeutic anticancer drug.


Assuntos
Amigdalina/farmacologia , Survivina/efeitos dos fármacos , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/efeitos dos fármacos , Células A549/efeitos dos fármacos , Amigdalina/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7/efeitos dos fármacos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Survivina/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
20.
Eur J Nutr ; 58(4): 1687-1701, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29785640

RESUMO

PURPOSE: These days, obesity threatens the health for which one of the main interventions is calorie restriction (CR). Due to the difficulty of compliance with this treatment, CR mimetics such as resveratrol (RSV) have been considered. The present study compared the effects of RSV and CR on hypothalamic remodeling in a diet-switching experiment. METHODS: C57BL/6 male mice received high-fat diet (HFD) for 4 weeks, subsequently their diet switched to chow diet, HFD + RSV, chow diet + RSV or CR diet for a further 6 weeks. Body weight, fat accumulation, hypothalamic apoptosis and expression of trophic factors as well as generation and fate specification of newborn cells in arcuate nucleus (ARC) were evaluated. RESULTS: Switching diet to RSV-containing foods leading to weight and fat loss after 6 weeks. In addition, not only a significant reduction in apoptosis but also a considerable increase in production of newborn cells in ARC occurred following consumption of RSV-enriched diets. These were in line with augmentation of hypothalamic ciliary neurotrophic factor and leukemia inhibitory factor expression. Interestingly, RSV-containing diets changed the fate of newborn neurons toward generation of more proopiomelanocortin than neuropeptide Y neurons. The CR had effects similar to those of RSV-containing diets in the all-evaluated aspects besides neurogenesis in ARC. CONCLUSIONS: Although both RSV-containing and CR diets changed the fate of newborn neurons to create an anorexigenic architecture for ARC, newborn neurons were more available after switching to RSV-enriched diets. It can be consider as a promising mechanism for future investigations.


Assuntos
Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Restrição Calórica/métodos , Dieta Hiperlipídica/efeitos adversos , Neurogênese/efeitos dos fármacos , Obesidade/dietoterapia , Resveratrol/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Resveratrol/administração & dosagem
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