RESUMO
In the search for pharmaceutically active compounds from natural products, it is crucial and challenging to develop separation or purification methods that target not only structurally similar compounds but also those with specific pharmaceutical functions. The adsorption-based method is widely employed in this field and holds potential for this application, given the diverse range of functional monomers that can be chosen based on structural or functional selectivity. In this work, an imidazolium ionic liquid (IL) modified paper membrane was synthesized via microwave reaction. Caffeic acid (CA), with potential interactions with imidazolium IL and a representative component of phenolic acids in Taraxaci Herba, was chosen as a target compound. After optimization of synthesis and extraction parameters, the resulting extraction membrane could be used to quantitatively analyze CA at ng/ml level, and to extract CA's analogues from the sample matrix. Cheminformatics confirmed the presence of structural and functional similarity among these extracted compounds. This study offers a novel approach to preparing a readily synthesized extraction membrane capable of isolating compounds with structural and functional analogies, as well as developing a membrane solid-phase extraction-based analytical method for natural products.
Assuntos
Ácidos Cafeicos , Imidazóis , Líquidos Iônicos , Membranas Artificiais , Ácidos Cafeicos/química , Ácidos Cafeicos/isolamento & purificação , Líquidos Iônicos/química , Imidazóis/química , Papel , Extração em Fase Sólida/métodos , Limite de Detecção , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Hepatic fibrosis is a common consequence of chronic liver diseases without approved antifibrotic therapies. Long noncoding RNAs (lncRNAs) play an important role in various pathophysiological processes. However, the functions of certain lncRNAs involved in mediating the antifibrotic role remain largely unclear. METHODS: The RNA level of lnc-High Expressed in Liver Fibrosis (Helf) was detected in both mouse and human fibrotic livers. Furthermore, lnc-Helf-silenced mice were treated with carbon tetrachloride (CCl4) or bile duct ligation (BDL) to investigate the function of lnc-Helf in liver fibrosis. RESULTS: We found that lnc-Helf has significantly higher expression in human and mouse fibrotic livers as well as M1 polarized hepatic macrophages (HMs) and activated hepatic stellate cells (HSCs). In vivo studies showed that silencing lnc-Helf by AAV8 vector alleviates CCl4- and BDL-induced hepatic inflammation and fibrosis. Furthermore, in vitro experiments revealed that lnc-Helf promotes HSCs activation and proliferation, as well as HMs M1 polarization and proliferation in the absence or presence of cytokine stimulation. Mechanistically, our data illustrated that lnc-Helf interacts with RNA binding protein PTBP1 to promote its interaction with PIK3R5 mRNA, resulting in increased stability and activating the AKT pathway, thus promoting HSCs and HMs activation and proliferation, which augments hepatic inflammation and fibrosis. CONCLUSION: Our results unveil a lnc-Helf/PTBP1/PIK3R5/AKT feedforward, amplifying signaling that exacerbates the process of hepatic inflammation and fibrosis, thus providing a possible therapeutic strategy for hepatic fibrosis.
Assuntos
Fosfatidilinositol 3-Quinase , RNA Longo não Codificante , Animais , Humanos , Camundongos , Células Cultivadas , Ribonucleoproteínas Nucleares Heterogêneas/genética , Inflamação , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Fatores de Transcrição/metabolismo , Fosfatidilinositol 3-Quinase/metabolismoRESUMO
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases. The dysregulation of liver sinusoidal endothelial cell (LSEC) phenotype is a critical early event in the fibrotic process. However, the biological function of lncRNAs in LSEC still remains unclear. METHODS: The expression level of lncRNA Airn was evaluated in both human fibrotic livers and serums, as well as mouse fibrotic livers. Gain- and loss-of-function experiments were performed to detect the effect of Airn on LSEC differentiation and hepatic stellate cell (HSC) activation in liver fibrosis. Furthermore, RIP, RNA pull-down-immunoblotting, and ChIP experiments were performed to explore the underlying mechanisms of Airn. RESULTS: We have identified Airn was significantly upregulated in liver tissues and LSEC of carbon tetrachloride (CCl4)-induced liver fibrosis mouse model. Moreover, the expression of AIRN in fibrotic human liver tissues and serums was remarkably increased compared with healthy controls. In vivo studies showed that Airn deficiency aggravated CCl4- and bile duct ligation (BDL)-induced liver fibrosis, while Airn over-expression by AAV8 alleviated CCl4-induced liver fibrosis. Furthermore, we revealed that Airn maintained LSEC differentiation in vivo and in vitro. Additionally, Airn inhibited HSC activation indirectly by regulating LSEC differentiation and promoted hepatocyte (HC) proliferation by increasing paracrine secretion of Wnt2a and HGF from LSEC. Mechanistically, Airn interacted with EZH2 to maintain LSEC differentiation through KLF2-eNOS-sGC pathway, thereby maintaining HSC quiescence and promoting HC proliferation. CONCLUSIONS: Our work identified that Airn is beneficial to liver fibrosis by maintaining LSEC differentiation and might be a serum biomarker for liver fibrogenesis.
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RNA Longo não Codificante , Animais , Biomarcadores/metabolismo , Tetracloreto de Carbono/metabolismo , Tetracloreto de Carbono/farmacologia , Células Endoteliais/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/farmacologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Camundongos , RNA Longo não Codificante/genéticaRESUMO
Calotropis gigantea is often found in mining areas with heavy metal pollution. However, little is known about the physiological and molecular response mechanism of C. gigantea to Cd stress. In the present study, Cd tolerance characteristic of C. gigantea and the potential mechanisms were explored. Seed germination test results showed that C. gigantea had a certain Cd tolerance capacity. Biochemical and transcriptomic analysis indicated that the roots and leaves of C. gigantea had different responses to early Cd stress. A total of 176 and 1618 DEGs were identified in the roots and leaves of C. gigantea treated with Cd compared to the control samples, respectively. Results indicated that oxidative stress was mainly initiated in the roots of C. gigantea, whereas the leaves activated several Cd detoxification processes to cope with Cd, including the upregulation of genes involved in Cd transport (i.e., absorption, efflux, or compartmentalization), cell wall remodeling, antioxidant system, and chelation. This study provides preliminary information to understand how C. gigantea respond to Cd stress, which is useful for evaluating the potential of C. gigantea in the remediation of Cd-contaminated soils.
Assuntos
Calotropis , Poluentes do Solo , Cádmio/análise , Cádmio/toxicidade , Calotropis/genética , Folhas de Planta/química , Folhas de Planta/genética , Raízes de Plantas/química , Raízes de Plantas/genética , Poluentes do Solo/toxicidade , TranscriptomaRESUMO
BACKGROUND: The purpose of this retrospective study was to evaluate the clinical efficacy of mineralized collagen (MC) versus anorganic bovine bone (Bio-Oss) for immediate implant placement in esthetic area. METHODS: Medical records of Department of Oral and Maxillofacial Surgery of Shandong Provincial Hospital were screened for patients who had been treated with immediate implant implantation in the esthetic area using either MC (Allgens®, Beijing Allgens Medical Science and Technology Co., Ltd., China) or Bio-Oss (Bio-Oss®, Geistlich Biomaterials, Wolhusen, Switzerland), between January 2018 and December 2019. All patients fulfilling the in-/exclusion criteria and following followed for a minimum period of 1 year after surgery were enrolled into the presented study. Implant survival rate, radiographic, esthetic and patient satisfactory evaluations were performed. RESULTS: Altogether, 70 patients were included in the study; a total of 80 implants were inserted. All implants had good initial stability. The survival rate of implants was 100% at 1-year follow-up. The differences in horizontal and vertical bone loss between the MC group (0.72 ± 0.26 mm, 1.62 ± 0.84 mm) and the Bio-Oss group (0.70 ± 0.52 mm, 1.57 ± 0.88 mm) were no significant difference statistically no significant 6 months after permanent restoration. Similar results occurred at 12 months after permanent restoration functional loaded. Clinical acceptability defined by pink esthetic score (PES) ≥ 6 (6.07 ± 1.62 vs. 6.13 ± 1.41) was not significantly different between groups. Patient satisfaction estimated by visual analog scale (VAS) was similar (8.56 ± 1.12 vs. 8.27 ± 1.44), and the difference was no significant difference between the two groups. CONCLUSIONS: The biomimetic MC showed a similar behaviour as Bio-Oss not only in its dimensional tissues changes but also in clinical acceptability and patient satisfaction. Within the limitations of this study, these cases show that MC could be considered as an alternative bone graft in IIP.
Assuntos
Substitutos Ósseos , Implantes Dentários , Animais , Substitutos Ósseos/uso terapêutico , Bovinos , Colágeno , Implantação Dentária Endóssea , Falha de Restauração Dentária , Estética Dentária , Humanos , Minerais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This study was designed to investigate the effect of 650-nm low-level laser irradiation (LLLI) as an adjunctive treatment of experimental periodontitis. To investigate possible LLLI-mediated anti-inflammatory effects, we utilized an experimental periodontitis (EP) rat model and analyzed c-Jun, c-Fos, ICAM-1, and CCL2 gene expressions on PB leukocytes and in the gingival tissue. Total RNA was isolated from the gingivae and peripheral blood (PB) leukocytes of normal, EP, scaling, and root planing (SRP)-treated EP and LLLI + SRP-treated EP rats, and gene expressions were analyzed by real-time PCR. The productions of c-Jun, c-Fos, ICAM-1, and CCL2 in gingivae were analyzed immunohistochemically. Tartrate-resistant acid phosphatase (TRAP) staining was used to determine osteoclast activity in alveolar bone. The c-Jun and ICAM-1 messenger RNA (mRNA) levels were significantly decreased in the EP rat gingival tissue treated by SRP + LLLI than by SRP, the c-Jun, ICAM-1, and c-Fos mRNA levels on PB leukocytes reduced after LLLI treatment but did not show any significant differences in both groups. There was no significant difference in CCL2 mRNA levels on PB leukocytes and in gingivae between the SRP + LLLI and the SRP groups. The c-Fos mRNA levels in gingivae did not show significant difference in both groups. Immunohistochemistry showed that the CCL2, ICAM-1, c-Jun, and c-Fos productions were significantly reduced in rats of the SRP + LLLI group compared with the only SRP group. LLLI significantly decreased the number of osteoclasts as demonstrated by TRAP staining. The 650-nm LLLI might be a useful treatment modality for periodontitis.
Assuntos
Quimiocina CCL2/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Terapia com Luz de Baixa Intensidade , Periodontite/metabolismo , Periodontite/radioterapia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Animais , Quimiocina CCL2/genética , Regulação da Expressão Gênica , Gengiva/metabolismo , Gengiva/patologia , Molécula 1 de Adesão Intercelular/genética , Masculino , Osteoclastos/patologia , Osteoclastos/efeitos da radiação , Periodontite/genética , Periodontite/patologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-jun/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-DawleyRESUMO
After publication of our article [1] we realized that we had not acknowledged that some of the text overlaps with a previous publication [2]. We apologize to readers for this error.
RESUMO
Evidence indicates that 1α, 25-dihydroxy vitamin D3 (1, 25-(OH)2D3) markedly reduces intraocular pressure (IOP) in nonhuman primates, while the biochemical mechanisms are unclear. To investigate the influence of oxidative stress on human trabecular meshwork cells (HTMCs) and the effect and regulatory mechanism of 1, 25-(OH)2D3 in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (H2O2) and showed that 1, 25-(OH)2D3 could inhibit oxidative stress-induced apoptosis and reduce extracellular matrix (ECM) composition of HTMCs. Moreover, 1, 25-(OH)2D3 could attenuate H2O2-induced inflammation in HTMCs. Mechanistically, our findings revealed that H2O2-induced damage was mediated by the transforming growth factor-ß (TGF-ß)-SMAD3 pathway in HTMCs, and 1, 25-(OH)2D3 could protect HTMCs against oxidative stress through vitamin D receptor (VDR), which antagonises the effects of SMAD3. Overall, these findings define a mechanism by which 1, 25-(OH)2D3 reduces ECM accumulation and suppresses the TGF-ß-SMAD3-VDR pathway in HTMCs, thus protecting the cells from oxidative stress, suggesting 1, 25-(OH)2D3 might be a potential therapeutic for glaucoma.
Assuntos
Calcitriol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Malha Trabecular/efeitos dos fármacos , Vitaminas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/metabolismo , Malha Trabecular/citologia , Malha Trabecular/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Vitamina D/análogos & derivados , Vitamina D/farmacologiaRESUMO
The intracellular delivery of biofunctional enzymes or therapeutic proteins through systemic administration is of great importance in therapeutic intervention of various diseases. However, current strategies face substantial challenges owing to various biological barriers, including susceptibility to protein degradation and denaturation, poor cellular uptake, and low transduction efficiency into the cytosol. Here, we developed a biomimetic nanoparticle platform for systemic and intracellular delivery of proteins. Through a biocompatible strategy, guest proteins are caged in the matrix of metal-organic frameworks (MOFs) with high efficiency (up to â¼94%) and high loading content up to â¼50 times those achieved by surface conjunction, and the nanoparticles were further decorated with the extracellular vesicle (EV) membrane with an efficiency as high as â¼97%. In vitro and in vivo study manifests that the EV-like nanoparticles can not only protect proteins against protease digestion and evade the immune system clearance but also selectively target homotypic tumor sites and promote tumor cell uptake and autonomous release of the guest protein after internalization. Assisted by biomimetic nanoparticles, intracellular delivery of the bioactive therapeutic protein gelonin significantly inhibits the tumor growth in vivo and increased 14-fold the therapeutic efficacy. Together, our work not only proposes a new concept to construct a biomimetic nanoplatform but also provides a new solution for systemic and intracellular delivery of protein.
Assuntos
Portadores de Fármacos/química , Vesículas Extracelulares/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Proteínas Inativadoras de Ribossomos Tipo 1/química , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Materiais Biomiméticos/uso terapêutico , Materiais Biomiméticos/toxicidade , Linhagem Celular Tumoral , Membrana Celular/química , Membrana Celular/metabolismo , Portadores de Fármacos/metabolismo , Portadores de Fármacos/uso terapêutico , Portadores de Fármacos/toxicidade , Endocitose/fisiologia , Vesículas Extracelulares/metabolismo , Humanos , Estruturas Metalorgânicas/metabolismo , Estruturas Metalorgânicas/uso terapêutico , Estruturas Metalorgânicas/toxicidade , Camundongos , Nanopartículas/metabolismo , Nanopartículas/uso terapêutico , Nanopartículas/toxicidade , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Proteínas Inativadoras de Ribossomos Tipo 1/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
TUG1 has been shown to be involved in diverse human diseases by regulating gene expression at transcriptional and post-transcriptional levels via interaction with miRNA or proteins. However, the role of TUG1 in liver fibrosis remains unclear. Here, we found that Tug1 is dysregulated in liver fibrosis according to the microarray analysis. Moreover, we investigated the expression files of Tug1 by using CCl4-and BDL-induced liver fibrosis model mice as well as in the primary cells isolated from the mice. We demonstrated that Tug1 is over-expressed in the fibrotic livers and activated HSCs, but not injured hepatocytes. In addition, we assessed the function of Tug1 in HSCs and found that Tug1 promotes the expression of α-SMA, Col1α1, Mmp2/9/10 and Timp1. Mechanically, Tug1 promotes the expression of these pro-fibrogenic genes by down-regulating miR-29b, thus accelerating the progression of liver fibrosis. Further study revealed that TUG1was up-regulated in liver tissues of patients with cirrhosis. All together, our data indicate that TUG1 might be a potential therapy target of liver fibrosis.
Assuntos
Regulação para Baixo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Células Cultivadas , Células HEK293 , Humanos , MicroRNAs/genética , RNA Longo não Codificante/genéticaRESUMO
Driven by the demands for contactless stress detection, technologies are being used for shape control when producing cold-rolled strips. This paper presents a novel contactless stress detection technology based on a magnetoresistance sensor and the magnetoelastic effect, enabling the detection of internal stress in manufactured cold-rolled strips. An experimental device was designed and produced. Characteristics of this detection technology were investigated through experiments assisted by theoretical analysis. Theoretically, a linear correlation exists between the internal stress of strip steel and the voltage output of a magneto-resistive sensor. Therefore, for this stress detection system, the sensitivity of the stress detection was adjusted by adjusting the supply voltage of the magnetoresistance sensor, detection distance, and other relevant parameters. The stress detection experimental results showed that this detection system has good repeatability and linearity. The detection error was controlled within 1.5%. Moreover, the intrinsic factors of the detected strip steel, including thickness, carbon percentage, and crystal orientation, also affected the sensitivity of the detection system. The detection technology proposed in this research enables online contactless detection and meets the requirements for cold-rolled steel strips.
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Accumulation of amyloid ß protein (Aß)-containing neuritic plaques in the brain is a neuropathological feature of Alzheimer's disease (AD). The ß-site APP-cleaving enzyme 1 (BACE1) is essential for Aß generation and dysregulation of BACE1 expression may lead to AD pathogenesis. Bcl-2-associated athanogen 1M (BAG-1M), initially identified as an anti-apoptotic protein, has also been found to be highly expressed in the same neurons that contain intracellular amyloid in the hippocampus of AD patient. In this report, we found that over-expression of BAG-1M enhances BACE1-mediated cleavage of amyloid precursor protein (APP) and Aß production by up-regulating BACE1 gene transcription. The regulation of BACE1 transcription by BAG-1M was dependent on NF-κB, as BAG-1M complexes NF-κB at the promoter of BACE1 gene and co-activates NF-κB-facilitated BACE1 transcription. Moreover, expression of BAG-1M by lentiviral vector in the hippocampus of AD transgenic model mice promotes Aß generation and formation of neuritic plaque, and subsequently accelerates memory deficits of the mice. These results provide evidence for an emerging role of BAG-1M in the regulation of BACE1 expression and AD pathogenesis and that targeting the BAG-1M-NF-κB complex may provide a mechanism for inhibiting Aß production and plaque formation.
Assuntos
Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/biossíntese , Precursor de Proteína beta-Amiloide/biossíntese , Ácido Aspártico Endopeptidases/biossíntese , Proteínas de Ligação a DNA/metabolismo , Transtornos da Memória/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Ácido Aspártico Endopeptidases/genética , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Humanos , Transtornos da Memória/genética , Transtornos da Memória/patologia , Camundongos , Camundongos Transgênicos , Fatores de Transcrição/genéticaRESUMO
Cervical cancer is one of the most common female cancers worldwide. Although the therapeutic outcomes of patients with early-stage cervical cancer have been significantly improved in the past decades, tumor metastasis and recurrence remain the major causes of cervical cancer-related deaths. In cervical squamous cell carcinoma (SCC), the aberrant activation of epithelial-mesenchymal transition (EMT), a crucial process in invasion and metastasis of epithelial cancer, could promote lymph nodal metastasis and recurrence, and predicts poor prognosis. In this study, we show that the expression levels of EMT markers, ß-catenin and Vimentin, are associated with the p63 isoform ΔNp63α in SCC by using immunohistochemistry staining and analysis. Compared to the control SiHa cells (SiHa-NC), the expression of E-cadherin and ß-catenin are upregulated, while Vimentin and ZEB1 are downregulated in the constructed SiHa cell line with stable ΔNp63α overexpression (SiHa-ΔNp63α). Besides, the migration and invasion abilities are also suppressed in SiHa-ΔNp63α cells with a typical epithelial morphology with cobblestone-like shape, suggesting that ΔNp63α is a vital EMT repressor in SCC cells. In addition, the involvement of miR-205/ZEB1 axis in the inhibition effect of ΔNp63α on EMT program is revealed by a miRNA array and confirmed by the subsequent transfection of the miR-205 mimic and antagomir. Moreover, SCC patients with low ΔNp63α expression and high EMT level show more frequent metastasis and recurrence as well as reduced overall survival. Therefore, EMT program and its vital repressor ΔNp63α could be used as biomarkers for tumor metastasis and recurrence in cervical cancer.
Assuntos
Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal , MicroRNAs/genética , Proteínas de Neoplasias/fisiologia , RNA Neoplásico/genética , Fatores de Transcrição/fisiologia , Proteínas Supressoras de Tumor/fisiologia , Neoplasias do Colo do Útero/patologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/fisiologia , Adulto , Antagomirs/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Prognóstico , Isoformas de Proteínas/fisiologia , Proteínas Recombinantes de Fusão/metabolismo , Transfecção , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/mortalidade , Vimentina/biossíntese , Vimentina/genética , beta Catenina/biossíntese , beta Catenina/genéticaRESUMO
BACKGROUND: Dexmedetomidine (DEX) has inherent neuroprotective properties that have been attributed to the activation of prosurvival kinases. However, the impact of supraclinical doses of DEX on neuroapoptosis and neuronal viability has not been determined. METHODS: Rat pups and primary neuronal cells were treated with DEX or ketamine (KET) alone or in combination. Neuroapoptosis was measured by cleaved-caspase-3 expression and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining in brain sections. Expression of prosurvival kinases was measured by Western blot. We measured the impact of DEX with and without α1-adrenergic receptor blockade on the viability of primary neuronal cell cultures. RESULTS: Increasing the cumulative dose of DEX resulted in elevated levels of neuroapoptosis in vivo. Low doses increased, whereas high dose decreased phosphorylation of the prosurvival kinases. KET alone and in combination with DEX produced a greater degree of apoptosis and reductions in expression of these protein kinases than DEX alone. Increasing concentrations of DEX decreased, while coadministration of an α1-adrenergic receptor blocker preserved neuronal viability in vitro. CONCLUSIONS: Although DEX is neuroprotective at clinical doses, high cumulative doses and concentrations induce neuroapoptosis, in vivo and in vitro, respectively. Because the current dosing schedules used in humans yield plasma levels that are substantially below concentrations that induce neurotoxicity, low-dose DEX should not be neurotoxic and has the potential to be a neuroprotective adjuvant.
Assuntos
Apoptose/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/toxicidade , Neurônios/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/toxicidade , Neurônios/patologia , Neurônios/fisiologia , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
We employed terahertz (THz) time-domain spectroscopy (TDS) imaging technology, a new nondestructive testing method, to detect the inclusions of glass-fiber-reinforced polymer (GFRP) composites. The refractive index and absorption coefficient of two types of GFRP composites (epoxy GFRP composites and polyester GFRP composites) were first extracted, and GFRP composites with Teflon inclusions were examined, including an epoxy GFRP solid panel with a smaller Teflon inclusion hidden behind a larger Teflon inclusion, and polyester GFRP solid panels with Teflon inclusions of various sizes, at different depths. It was experimentally demonstrated that THz TDS imaging technology could clearly detect a smaller inclusion hidden behind a larger inclusion. When the reflected THz pulse from the inclusion did not overlap with that from the front surface of the sample, removal of the latter before Fourier transform was shown to be helpful in imaging the inclusions. With sufficiently strong incident THz radiation, inclusion insertion depth had little impact on the ability of the THz wave to detect inclusions. However, as the thickness of the inclusion became thinner, the inclusion detection ability of the THz wave deteriorated. In addition, with a combination of reflected C-scan imaging and B-scan imaging using the reflected time-domain waveform, both the lateral sizes and locations of the inclusions and the depths and thicknesses of the inclusions were clearly ascertained.
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Terahertz (THz) time-domain spectroscopy (TDS) imaging is considered a nondestructive evaluation method for composite materials used for examining various defects of carbon fiber reinforced polymer (CFRP) composites and fire-retardant coatings in the reflective imaging modality. We demonstrate that hidden defects simulated by Teflon artificial inserts are imaged clearly in the perpendicular polarization mode. The THz TDS technique is also used to measure the thickness of thin fire-retardant coatings on CFRP composites with a typical accuracy of about 10 micrometers. In addition, coating debonding is successfully imaged based on the time-delay difference of the time-domain waveforms between closely adhered and debonded sample locations.
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Optical parameters which macroscopically characterize optical properties of materials indirectly reflect microscopic peculiarities of materials. Accurate extractions of optical parameters are significant for the research of microscopic behavior and macroscopic responses of materials. In recent years, as a new spectral analysis method, terahertz time-domain spectroscopy (THz-TDS) technology has become a research hotspot. Due to the low THz radiation energy and narrow pulse width (picosecond range), THz-TDS technology is nondestructive with high-temporal-resolution when being used to extract optical parameters of samples. This paper summarizes optical parameters extraction methods by using THz transmission and reflection spectroscopy technology, emphatically introduces several classic methods and analyses, along with their respective merits and demerits, and finally discusses the challenges of THz-TDS technology in optical parameters extraction. In conclusion, the transmission methods are adaptive for measuring substances which slightly absorb terahertz radiation, whereas the reflection methods are suitable for measuring materials with strong absorption capacity.
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Osteoarthritis is a common arthritis disease caused by cartilage tissue damage and degeneration, which is one of the large epidemics that affect human health. The early detection of the pathological changes of articular cartilage can greatly improve the cure rate of disease, but the relevant clinical diagnosis technology has not been developed. In recent years, the applications and researches of terahertz technology are increasingly valued and it has drawn great attention in the field of medicine. Compared with traditional methods, the terahertz radiation is low-energy and non-ionizing whose spectral-fingerprinting capability is well-known in the biological world. Meanwhile, THz technology has a great potential in diagnosis of articular cartilage early degeneration. This paper briefly introduces the physiological and pathological conditions of the articular cartilage, the current clinical techniques of articular cartilage detection. It mainly summarizes the terahertz technology used for detecting articular cartilage, including detection of animal and human cartilage respectively. At last, the challenges and development prospects of terahertz technology in articular cartilage detection are discussed.
Assuntos
Cartilagem Articular , Animais , Humanos , Osteoartrite , Radiação TerahertzRESUMO
Epoxy resin is an important adhesive applied in the manufacturing processes of fiber reinforced polymer (FRP) composites. Terahertz (THz) time-domain spectroscopy (TDS) technology is an effective supplementary method for nondestructive evaluation (NDE) of FRP composites. As one of the most important parameters for epoxy resin, different curing temperature can affect the properties of epoxy resin. In this paper, we carry out systematic investigations on THz transmission properties of epoxy resin cured respectively under room temperature and high temperature with THz TDS technology. At the same time, the authors extract the refractive indices and absorption coefficients of epoxy resin, and make comparisons d. As shown in the experiments, the epoxy resin samples cured under room temperature have no bubble, whereas there are some micro-bubbles in the samples cured under high temperature, which reduce the sample density. Hence, the refractive index and absorption coefficient of epoxy resin cured under room temperature are both greater than those cured under high temperature. The difference of refractive index of different samples cured under the same condition is not significant. In addition, the difference of absorption coefficient of different samples cured under room temperature is also slight. However, the difference of absorption coefficient of different samples cured under high temperature gradually increase within the frequency from 0.6 to 1.5 THz, which is mainly due to the heterogeneous distribution of the bubbles in the different samples cured under high temperature. Moreover, the absorption coefficient of epoxy resin prepared under both curing temperatures gradually increases with the frequency, and there is no obvious absorption peak. Finally, because of the existence of Fabry-Pérot interference, the power transmission ratio of thicker epoxy resin samples may be greater than thinner samples at the resonant frequency. This research is of great significance for the THz NDE of FRP composites.
RESUMO
The Hippo pathway was originally identified and named through screening for mutations in Drosophila, and the core components of the Hippo pathway are highly conserved in mammals. In the Hippo pathway, MST1/2 and LATS1/2 regulate downstream transcription coactivators YAP and TAZ, which mainly interact with TEAD family transcription factors to promote tissue proliferation, self-renewal of normal and cancer stem cells, migration, and carcinogenesis. The Hippo pathway was initially thought to be quite straightforward; however, recent studies have revealed that YAP/TAZ is an integral part and a nexus of a network composed of multiple signaling pathways. Therefore, in this review, we will summarize the latest findings on events upstream and downstream of YAP/TAZ and the ways of regulation of YAP/TAZ. In addition, we also focus on the crosstalk between the Hippo pathway and other tumor-related pathways and discuss their potential as therapeutic targets.