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1.
Small ; : e2402729, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39077957

RESUMO

Interface design has enormous potential for the enhancement of interfacial polarization and microwave absorption properties. However, the construction of interfaces is always limited in components of a single dimension. Developing systematic strategies to customize multidimensional interfaces and fully utilize advantages of low-dimensional materials remains challenging. Two-dimensional transition metal dichalcogenides (TMDCs) have garnered significant attention owing to their distinctive electrical conductivity and exceptional interfacial effects. In this study, a series of hollow TMDCs@C fibers are synthesized via sacrificial template of CdS and confined growth of TMDCs embedded in the fibers. The complex permittivity of the hollow TMDCs@C fibers can be adjusted by tuning the content of CdS templates. Importantly, the multidimensional interfaces of the fibers contribute to elevating the microwave absorption performance. Among the hollow TMDCs@C fibers, the minimum reflection loss (RLmin) of the hollow MoS2@C fibers can reach -52.0 dB at the thickness of 2.5 mm, with a broad effective absorption bandwidth of 4.56 GHz at 2.0 mm. This work establishes an alternative approach for constructing multidimensional coupling interfaces and optimizing TMDCs as microwave absorption materials.

2.
FASEB J ; 37(7): e22974, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37249328

RESUMO

Given the important role of m6A, the most common and reversible mRNA modification, in the pathogenesis of ischemic stroke, this study investigates the mechanisms of m6A methyltransferase METTL3 in neuronal damage in ischemic stroke. In silico analysis was used to pinpoint the expression of ANXA2, which was verified in clinical peripheral blood samples. SD rats were used for middle cerebral artery occlusion (MCAO) establishment. The experimental data suggested that T lymphocytes were increased in peripheral blood samples of ischemic stroke patients and MCAO rats. The MCAO rats were treated with anti-ANXA2 alone or combined with RP101075 (T lymphocyte infiltration inhibitor), followed by brain injury assessment. Oxygen-glucose deprivation/reoxygenation (OGD/R) was induced in primary cortical neurons, where shRNAs targeting ANXA2 or METTL3, or overexpression plasmids of METTL3 were introduced to verify the regulatory function for METTL3. Inhibition of T lymphocyte migration to the ischemic brain reduced brain injury in MCAO rats and neuronal damage in OGD/R-exposed neurons. Ablation of ANXA2 in T lymphocytes inhibited the migration of T lymphocytes to the ischemic brain and reduced neuronal damage. Mechanistically, METTL3 reduced ANXA2 expression in T lymphocytes through m6A modification and inhibited p38MAPK/MMP-9 pathway activation, exerting protective effects against neuronal damage in ischemic stroke. Overall, this study reveals the neuroprotective effects of METTL3-mediated ANXA2/p38MAPK/MMP-9 inhibition against ischemic stroke.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Ratos , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Metaloproteinase 9 da Matriz , Neuroproteção , Ratos Sprague-Dawley , Acidente Vascular Cerebral/patologia , Humanos
3.
Neurol Sci ; 45(5): 2063-2073, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38049551

RESUMO

OBJECTIVE: This study aimed to examine the volumes of thalamic nuclei and the intrinsic thalamic network in patients with Wilson's disease (WDs), and to explore the correlation between these volumes and the severity of neurological symptoms. METHODS: A total of 61 WDs and 33 healthy controls (HCs) were included in the study. The volumes of 25 bilateral thalamic nuclei were measured using structural imaging analysis with Freesurfer, and the intrinsic thalamic network was evaluated through structural covariance network (SCN) analysis. RESULTS: The results indicated that multiple thalamic nuclei were smaller in WDs compared to HCs, including mediodorsal medial magnocellular (MDm), anterior ventral (AV), central median (CeM), centromedian (CM), lateral geniculate (LGN), limitans-suprageniculate (L-Sg), reuniens-medial ventral (MV), paracentral (Pc), parafascicular (Pf), paratenial (Pt), pulvinar anterior (PuA), pulvinar inferior (PuI), pulvinar medial (PuM), ventral anterior (VA), ventral anterior magnocellular (VAmc), ventral lateral anterior (VLa), ventral lateral posterior (VLp), ventromedial (VM), ventral posterolateral (VPL), and right middle dorsal intralaminar (MDI). The study also found a negative correlation between the UWDRS scores and the volume of the right MDm. The intrinsic thalamic network analysis showed abnormal topological properties in WDs, including increased mean local efficiency, modularity, normalized clustering coefficient, small-world index, and characteristic path length, and a corresponding decrease in mean node betweenness centrality. WDs with cerebral involvement had a lower modularity compared to HCs. CONCLUSIONS: The findings suggest that the majority of thalamic nuclei in WDs exhibit significant volume reduction, and the atrophy of the right MDm is closely related to the severity of neurological symptoms. The intrinsic thalamic network in WDs demonstrated abnormal topological properties, indicating a close relationship with neurological impairment.


Assuntos
Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/diagnóstico por imagem , Núcleos Talâmicos/diagnóstico por imagem , Tálamo/diagnóstico por imagem
4.
Small ; 19(6): e2205407, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36461729

RESUMO

Structural engineering via the template method is efficient for micro-nano assembling. However, only structural design and lack of composition control restrict their advanced application. To overcome this issue, applying a template to simultaneously realize the structural design and fine component control is highly desired, which has been ignored. In this study, a spinel-shaped MoS2 heterostructure with controlled phase ratios of 1H and 2H phase is developed using the AlOOH template method. This work demonstrates that the MoS2 phase transition mechanism from 2H to 1T is substantially attributed to the close exposed crystal's surface and approximately accordant surface energy. The superiority and additional proof are provided based on density-functional theory simulation, transmission electron microscope holography, etc. With an effective absorptance region of 6.3 GHz under a thickness of 1.4 mm, the reported samples present outstanding microwave absorption capacity. This is attributed to the beneficial coupled effect between the well-designed structure and phase regulation. This work offers valuable insights into structural engineering and component regulation template methods.

5.
Ecotoxicol Environ Saf ; 258: 114955, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37121076

RESUMO

The effect of mean flow velocity on phosphorus (P) partitioning between water and sediment has received much attention in recent decades. However, the impact of turbulence on the efficiency and capability of sediment adsorbing and desorbing dissolved inorganic phosphorus (DIP) is still unclear. A series of contrasting experiments on the sediment sorption and desorption of DIP with the flow turbulence kinetic energy (TKE) ranging from 1.95 to 2.93 pa have been conducted. It was found that the adsorbed P onto unit mass of sediment increases with the increase in TKE. It is because an increase in TKE results in a rise in the effective adsorption capacity of sediment (bm) by 20-30% during the adsorption process. The bm shows the maximum rise from 0.18 to 0.25 mg/g when TKE increases from 1.95 to 2.93 pa with a fixed sediment concentration of 0.5 g/L. To account for the direct effect of TKE on P adsorption, the Langmuir model is modified by introducing a newly defined coefficient (fA-TKE). The fA-TKE shows a good linear relationship with TKE. Comparison between the modified model and the classic model shows that the amount of adsorbed P could be overestimated by over 50% if the direct effect of turbulence intensity is ignored. The experimental data show that the increase in TKE also enhances the desorption process, with the degree of P desorption (Ddes) increased by 44%. The relation between Ddes and TKE can be well represented using a logarithmic function to quantify the direct effect of turbulence intensity on desorption of P.


Assuntos
Fósforo , Poluentes Químicos da Água , Sedimentos Geológicos , Adsorção , Água , Poluentes Químicos da Água/análise
6.
Surg Today ; 53(6): 736-742, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36335219

RESUMO

PURPOSE: Postoperative delirium (POD) commonly occurs after major abdominal surgery and is associated with increased morbidity and mortality. There have been many studies on the relationship between POD and various surgeries, but research on POD after pancreatic cancer surgery is limited. The aim of this study was to identify the incidence and risk factors of POD after pancreatic cancer surgery. METHODS: The subjects of this retrospective analysis were 196 patients who were transferred for postoperative care after pancreatic cancer surgery, to a 12-bed critical care medicine ward at Shandong Provincial Hospital, affiliated with Shandong First Medical University, between January 2015 and December 2019. The patients were divided according to whether they suffered POD into a delirium group and a non-delirium group. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit and two independent medical practitioners analyzed all the data. Univariate and multiple logistic regression analyses were performed. RESULTS: The overall delirium incidence was 20.41%, which increased to 29.03% for patients aged ≥ 70 years. POD was associated with age, smoking, the American Society of Anesthesiologists classification, the Acute Physiology and Chronic Health Evaluation II score, and the TNM stage of the cancer. The variables concerning sex, drinking, hypertension, a history of cerebral disease, surgery type, operation time, amount of bleeding, and the intraoperative use of dexmedetomidine did not differ significantly between the two groups. There was no significant difference in the length of ICU stay, with the exclusion of long-term stay for complications, between the groups, but POD tended to prolong the postoperative hospital stay and increase the risk of mortality. There was also a gradual decline in the incidence of POD between 2015 and 2019, especially from 2015 to 2018, after preventive measures were implemented. CONCLUSION: POD is related to many risk factors and worthy of attention. Appropriate management can reduce its incidence or at least shorten its duration.


Assuntos
Delírio do Despertar , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Incidência , Fatores de Risco , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas
7.
Small ; 18(3): e2104380, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34914181

RESUMO

Hierarchical hollow structure with unique interfacial properties holds great potential for microwave absorption (MA). Ti3 C2 Tx MXene has been a hot topic due to rich interface structure, abundant defects, and functional groups. However, its overhigh permittivity and poor aggregation-resistance limit the further application. Herein, a hierarchical MXene-based hollow microsphere is prepared via a facile spray drying strategy. Within the microsphere, few-layered MXene nanosheets are separated by dispersed carbon nanotubes (CNTs), exposing abundant dielectric polarization interfaces. Besides, numerous magnetic Fe3 O4 nanospheres are uniformly dispersed and confined within nano-cavities between 1D network and 2D framework. Such a novel structure simultaneously promotes interfacial polarization by ternary MXene/CNTs/Fe3 O4 interfaces, enhances magnetic loss by microscale and nanoscale coupling network, enlarges conduction loss by MXene/CNTs dual-network, and optimizes impedance matching by hierarchical porous structure. Therefore, Fe3 O4 @Ti3 C2 Tx /CNTs composite achieves excellent MA property with a maximum reflection loss of -40.1 dB and an effective bandwidth of 5.8 GHz at the thickness of only 2 mm. This work demonstrates a feasible hierarchical structure design strategy for multi-dimension MXene composite to realize the high-efficiency MA performance.

8.
Small ; 17(46): e2103351, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34651430

RESUMO

The advancement of electromagnetic (EM) protection technology promotes the urgent demand for the structural design of electromagnetic functional materials. Here, tadpole-like Fe@SiO2 @C-Ni (FSCN) composites with magnetic core-shell and nonspherical hollow architectures through multiple hydrolysis-polymerization reactions are reported. The Fe core and well-distributed Ni nanoparticles greatly promote the magnetic properties of FSCN and construct a multiscale magnetic coupling network. Meanwhile, the multishell composites consisting of carbon shell with Ni decorated possess an abundance of heterogeneous interfaces, generating effective interfacial polarization and relaxation. The hollow feature and the coordination of magnetic and dielectric capacities offer an optimized impedance balance, providing a fundament for the microwaves propagating into the absorber. Owing to the attractive effects resulted from the deliberate tadpole-like structure design, the FSCN composites ensure an effective EM energy conversion at the high-frequency region, which obtain the strongest reflection loss value of -45.2 dB and the extremely broad effective absorption bandwidth of 13.1 GHz. This work provides an important solution for magnetic-dielectric nanostructure design for microwave absorption and energy conversion materials.

9.
Inflamm Res ; 70(7): 835-846, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34216220

RESUMO

Diabetic nephropathy (DN) seriously affects the people's life and health in China. This study aimed to investigate the effect of circRNA circ-ITCH on improving DN by regulating the miR-33a-5p/SIRT6 axis and the possible mechanism of action. High glucose (HG)-induced rat mesangial cells (RMCs) were used to simulate the DN in vitro. Reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis were conducted to detect the gene or protein expression. Cell Counting Kit-8 (CCK-8) and wound healing assays were performed to estimate the cell viability and migration capability. Immunofluorescence and enzyme-linked immunosorbent assay (ELISA) were used to detect the α-Smooth Muscle Actin (α-SMA) expression and levels of inflammatory factors. The potential associations between circ-ITCH and miR-33a-5p, miR-33a-5p and SIRT6 in RMCs were measured via dual-luciferase reporter assay. Streptozotocin (STZ) was used to induce the diabetic mice. Blood glucose and serum insulin of mice were determined by corresponding kits, and blood urea nitrogen (BUN) and serum creatinine (SCr) were measured using an automatic biochemical analyzer. Hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining were applied to observe the degree of pathological injury and fibrosis of renal tissues. The results of the present study revealed that circ-ITCH expression was obviously decreased in HG-induced RMCs. In addition, circ-ITCH overexpression inhibited the viability, migration, fibrosis and inflammatory response of HG-induced RMCs. Further experiments confirmed that miR-33a-5p may be a direct target of circ-ITCH and SIRT6 may be a direct target of miR-33a-5p. Notably, the miR-33a-5p mimic or shRNA-SIRT6 were discovered to reverse the inhibitory effects of circ-ITCH on the proliferation, migration, fibrosis and inflammatory response of HG-induced RMCs. Furthermore, circ-ITCH overexpression ameliorated renal inflammation and fibrosis in STZ-induced diabetic mice. In conclusion, circ-ITCH alleviated renal inflammation and fibrosis in STZ-induced diabetic mice by regulating the miR-33a-5p/SIRT6 axis.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [ChunYang] Last name [Xu]. Author 2 Given name: [DingBo] Last name [Xu]. Author 3 Given name: [YongHua] Last name [Liu]. Author 4 Given name: [Juanjuan] Last name [Jiang]. Also, kindly confirm the details in the metadata are correct.ok.


Assuntos
Diabetes Mellitus Experimental/genética , MicroRNAs , RNA Circular , Sirtuínas/genética , Animais , Glicemia/análise , Nitrogênio da Ureia Sanguínea , Células Cultivadas , Creatinina/sangue , Citocinas/genética , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Fibrose , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Insulina/sangue , Rim/metabolismo , Rim/patologia , Masculino , Células Mesangiais/metabolismo , Camundongos , Ratos
10.
Addict Biol ; 26(6): e13062, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114299

RESUMO

Methamphetamine (METH) abuse has become a global public health problem. However, the potential mechanisms involving METH-induced metabolic disorders have thus far remained poorly understood. Metabolomics can provide a clue for the cause of apparent changes and consequently be used to investigate the METH-induced dysregulation of metabolite expression and the mechanism of metabolic disorder mechanism. This laboratory investigation included 80 METH abusers and 80 healthy people. The serum metabolites were detected and analysed by gas chromatography/time-of-flight mass spectrometry. Raw data were processed with the software MS DIAL, which includes deconvolution, peak alignment and compound identification. The data matrix was processed by univariate and multivariate analyses for significant metabolite screening with the criteria of variable importance in projection values > 1, fold change > 1.5 and the t test (p value < 0.05). Significant differences in 16 metabolites (deoxycholic acid, cholic acid, hydroxylamine, etc.) in serum were found between the METH abuse group and the control group. Energy metabolic pathways and several amino acid metabolic pathways (alanine, aspartic acid and glutamate metabolism and tryptophan metabolism) were primarily involved. Further analysis indicated that the area under the receiver operating characteristic curve (AUC) was 0.998 for these 16 metabolites. Among the metabolites, three carbohydrates (d-ribose, cellobiose and maltotriose) had an AUC of 0.975, which were determined as potential markers of abuse. We observed metabolic disturbances in METH abusers, particularly perturbation in energy metabolism and amino acid metabolism, which can provide new insights into the search for biomarkers and the mechanisms underlying the adverse effects of METH on human health.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , Doenças Metabólicas/induzido quimicamente , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica/métodos , Metanfetamina/efeitos adversos , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/sangue , Biomarcadores , Estudos Transversais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/fisiopatologia , Pessoa de Meia-Idade , Curva ROC
11.
BMC Genomics ; 21(1): 217, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32151246

RESUMO

BACKGROUND: Cyanobacteria are of special concern because they proliferate in eutrophic water bodies worldwide and affect water quality. As an ancient photosynthetic microorganism, cyanobacteria can survive in ecologically diverse habitats because of their capacity to rapidly respond to environmental changes through a web of complex signaling networks, including using second messengers to regulate physiology or metabolism. A ubiquitous second messenger, bis-(3',5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP), has been found to regulate essential behaviors in a few cyanobacteria but not Microcystis, which are the most dominant species in cyanobacterial blooms. In this study, comparative genomics analysis was performed to explore the genomic basis of c-di-GMP signaling in Microcystis aeruginosa. RESULTS: Proteins involved in c-di-GMP metabolism and regulation, such as diguanylate cyclases, phosphodiesterases, and PilZ-containing proteins, were encoded in M. aeruginosa genomes. However, the number of identified protein domains involved in c-di-GMP signaling was not proportional to the size of M. aeruginosa genomes (4.97 Mb in average). Pan-genome analysis showed that genes involved in c-di-GMP metabolism and regulation are conservative in M. aeruginosa strains. Phylogenetic analysis showed good congruence between the two types of phylogenetic trees based on 31 highly conserved protein-coding genes and sensor domain-coding genes. Propensity for gene loss analysis revealed that most of genes involved in c-di-GMP signaling are stable in M. aeruginosa strains. Moreover, bioinformatics and structure analysis of c-di-GMP signal-related GGDEF and EAL domains revealed that they all possess essential conserved amino acid residues that bind the substrate. In addition, it was also found that all selected M. aeruginosa genomes encode PilZ domain containing proteins. CONCLUSIONS: Comparative genomics analysis of c-di-GMP metabolism and regulation in M. aeruginosa strains helped elucidating the genetic basis of c-di-GMP signaling pathways in M. aeruginosa. Knowledge of c-di-GMP metabolism and relevant signal regulatory processes in cyanobacteria can enhance our understanding of their adaptability to various environments and bloom-forming mechanism.


Assuntos
GMP Cíclico/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Microcystis/metabolismo , Biologia Computacional , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Genômica , Microcystis/classificação , Microcystis/genética , Fósforo-Oxigênio Liases/genética , Fósforo-Oxigênio Liases/metabolismo , Filogenia , Domínios Proteicos , Transdução de Sinais
12.
Mol Carcinog ; 59(5): 492-502, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32128886

RESUMO

Gliomas are the most common malignant tumor in the central nervous system and are also one of the leading causes of death in cancer patients. Recently, mounting evidence suggested that both long noncoding RNAs (lncRNAs) and microRNAs play important roles in the proliferation and invasion of cancers, including gliomas. However, the role of lncRNA RP11-626G11.3 in glioma-genesis is still uncovered. Results indicated that lncRNA RP11-626G11.3 was up-regulated in glioma tissues and cell lines, moreover, its overexpression positively correlated with the poor prognosis and advanced pathological stages. Gain and loss of functional experiments demonstrated that lncRNA RP11-626G11.3 promoted the proliferation and invasion of glioma cells in vitro. The knockdown of lncRNA RP11-626G11.3 repressed the tumor growth in vivo. Mechanistically, lncRNA RP11-626G11.3 positively regulated the SP1 expression via competitively sponging with miR-375. Overall, our study shows that lncRNA RP11-626G11.3 promotes glioma progression by sponging miR-375 to regulate SP1 expression, which may provide a novel therapeutic strategy for glioma.


Assuntos
Biomarcadores Tumorais/metabolismo , Glioma/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição Sp1/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Progressão da Doença , Seguimentos , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Prognóstico , Fator de Transcrição Sp1/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Recept Signal Transduct Res ; 40(1): 58-66, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31997696

RESUMO

Purpose: Anisodamine (An) has anti-inflammatory effects, but its role in acute pancreatitis is still unknown. This study aimed to explore the action mechanism of An pretreatment in lipopolysaccharide (LPS)-induced pancreatic acinar cells, hoping to provide a research basis for the disease treatment.Materials and methods: Pancreatic acinar cells were pretreated with An at different concentrations and then induced by LPS. The viability and apoptosis of the treated cells were measured by Cell Counting Kit-8 and flow cytometry. The releases of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-18 were measured by enzyme-linked immunosorbent assay. The expressions of thioredoxin-interacting protein (TXNIP), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), NOD-like receptor protein 3 (NLRP3), Caspase-1, p65, and inhibitor of kappa B alpha (IκBα) in the treated cells were detected by Western blot and quantitative real-time polymerase chain reaction assay.Results: LPS promoted apoptosis of pancreatic acinar cells, suppressed cell viability, increased TNF-α, IL-1ß, and IL-18 releases and the expression levels of TXNIP, ASC, NLRP3, Caspase-1, p-p65, and p-IκBα, however, such effects of LPS could be alleviated by An pretreatment with the strongest effect when the concentration of An was set at 100 µg/mL. Moreover, overexpressed NLRP3 aggravated the effects of LPS in pancreatic acinar cells, which could be reversed by pretreatment of 100 µg/mL An.Conclusion: An pretreatment attenuated LPS-induced apoptosis and inflammatory response of pancreatic acinar cells through suppressing NLRP3 and inactivating NF-κB signaling pathway, thus, it could be explored as a potential therapy for treating acute pancreatitis.


Assuntos
Células Acinares/metabolismo , Células Acinares/patologia , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pâncreas/patologia , Transdução de Sinais , Alcaloides de Solanáceas/farmacologia , Células Acinares/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Inflamação/patologia , Lipopolissacarídeos , Ratos , Transdução de Sinais/efeitos dos fármacos
14.
Exp Cell Res ; 383(1): 111496, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306654

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide, and there is currently no effective therapeutic strategy in clinical practice. Gene therapy has great potential for decreasing tumor-induced mortality but has been clinically limited because of the lack of tumor-specific targets and insufficient gene transfer. The study of targeted transport of therapeutic genes in HCC treatment seems to be very important. In this study, we evaluated a gene therapy approach targeting HCC using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system in HCC cell lines and in an in vivo human HCC xenograft mouse model. GP73-modified liposomes targeted gene delivery to the tumor tissue, and the survivin promoter drove HSVtk expression in the HCC cells. Our results showed that the survivin promoter was specifically activated in tumor cells and HSVtk was expressed selectively in tumor cells. Combined with GCV treatment, HSVtk expression resulted in suppression of HCC cell proliferation via enhancing apoptosis. Moreover, tail vein injection of GP73-HSVtk significantly suppressed the growth of xenograft tumors through an apoptosis-dependent pathway and extended the survival of tumor-bearing mice without damaging the mice liver functions. Taken together, this study demonstrates an effective cancer-specific gene therapy strategy using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system for HCC that can be further developed for future clinical trials.


Assuntos
Carcinoma Hepatocelular/terapia , Terapia Genética , Lipossomos/administração & dosagem , Neoplasias Hepáticas/terapia , Proteínas de Membrana/química , Survivina/genética , Timidina Quinase/genética , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células , Feminino , Ganciclovir/administração & dosagem , Vetores Genéticos/administração & dosagem , Humanos , Lipossomos/química , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Regiões Promotoras Genéticas , Simplexvirus/enzimologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Cancer Control ; 26(1): 1073274819846593, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31046434

RESUMO

MicroRNAs (miRNAs), a subgroup of small noncoding RNAs, play critical roles in tumor growth and metastasis. Accumulating evidence shows that the dysregulation of miRNAs is associated with the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism by which miR-942-3p contributes to HCC remains undocumented. The association between miR-942-3p expression and the clinicopathological characteristics in HCC patients was analyzed by The Cancer Genome Atlas data set. The targets of miR-942-3p were identified by bioinformatic analysis and dual luciferase report assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays were performed to assess the functional role of miR-942-3p in HCC cells. Consequently, we found that miR-942-3p expression level was elevated in HCC tissues and cell lines as compared with the normal tissues and was associated with the pathological stage and tumor node metastasis (TNM) stage, acting as an independent prognostic factor of poor survival in patients with HCC. Ectopic expression of miR-942-3p enhanced the proliferation and invasive potential of HCC cells, but inhibition of miR-942-3p expression had the opposite effects. Mannose-binding lectin 2 (MBL2) was further identified as a direct target of miR-942-3p and possessed a negative correlation with miR-942-3p expression and unfavorable survival in patients with HCC. Restoration of MBL2 inhibited the progression of HCC cells and attenuated the tumor-promoting effects induced by miR-942-3p. In conclusion, miR-942-3p may act as an oncogenic factor in HCC cells by targeting MBL2 and provide a potential marker for patients with HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Lectina de Ligação a Manose/genética , MicroRNAs/genética , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Resultado do Tratamento
16.
Bioorg Chem ; 82: 1-5, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30267969

RESUMO

Five novel and rare cadinane-type sesquiterpene glycosides, cornucadinoside A-E (1-5) were isolated from water extract of the fruit of Cornus officinalis Sieb. et Zuuc.. The new chemical structures, together with their absolute configurations, were elucidated on the basis of extensive spectroscopic analysis, including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Their structures, which possess a naphthalene skeleton, are the first report on the occurrence of cadinane sesquiterpene glycosides in Cornus. Additionally, all the compounds exhibited marked α-glucosidase inhibitory activity except for 3in vitro.


Assuntos
Cornus/química , Frutas/química , Inibidores de Glicosídeo Hidrolases/química , Glicosídeos/química , Sesquiterpenos/química , Dicroísmo Circular , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosídeos/isolamento & purificação , Naftalenos/química , Naftalenos/isolamento & purificação , Sesquiterpenos/isolamento & purificação
17.
J Acoust Soc Am ; 145(5): 3208, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31153337

RESUMO

The aim of this study is to explore the performance of binaural and monaural recordings in soundscape evaluation. Twelve sites with different acoustic scenarios were chosen, where binaural and monaural recordings were simultaneously made. Nine soundscape indicators were assessed by residents through a laboratory-based auditory test. The results showed that the two recording methods present good agreement on most soundscape evaluation indicators including overall impression, acoustic comfort, pleasantness, annoyance, eventfulness, and loudness. The two recording methods were found to be correlated with different indicators in a similar way. For most sites, the two recording methods were significantly correlated excluding for directionality. For both recording methods, the A-weighted sound pressure level was found to have a weak impact on soundscape evaluation. Reverberation time significantly affects reverberance through binaural recordings. Overall, for most soundscape indicators, it is feasible to use both recording methods, although when "realism," "reverberance," and "directivity" are involved in evaluation, binaural recordings will render corresponding perception more consistently than the monaural.


Assuntos
Limiar Auditivo/fisiologia , Percepção Sonora/fisiologia , Som , Estimulação Acústica/métodos , Acústica , Testes Auditivos/métodos , Humanos
18.
J Med Syst ; 43(9): 298, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352647

RESUMO

The aim of this study was to investigate the alterations in regional homogeneity assessed by fMRI in patients with migraine without aura (MWoA). Fifty-six eligible MWoA patients and 32 matched healthy volunteers were enrolled in this study. MWoA patients were divided into three groups according to the headache days per month within 3 months: infrequent episodic migraine (IEM) group, frequent episodic migraine (FEM) group, and chronic migraine (CM) group. Data collection and rest-state fMRI examination were performed in all cases. The ReHo method was used to analyze the blood oxygen level dependent (BLOD) signals of the adjacent voxels in the brain regions of each patient, and the consistency of their fluctuations in the sequences of same time. Compared with normal controls, ReHo values of bilateral thalami, right insula and right middle temporal gyrus increased and both precentral gyri decreased in the IEM group; ReHo values of bilateral thalami and the right middle temporal gyrus increased; ReHo values of both anterior cingulate cortex, precentral gyri and putamen decreased in the FEM group. Compared with control group, ReHo values of left olfactory cortex, right hippocampus, parahippocampal gyrus, suboccipital gyrus and precuneus increased, both precentral gyri, precuneus, putamen and anterior cingulate cortex decreased in the CM group. Compared with IEM group, ReHo values of both putamen, left middle frontal gyrus, right superior frontal gyrus increased, and the left precuneus decreased in the FEM group. Compared with FEM group, ReHo values of left olfactory and left precuneus increased, and the right superior frontal gyrus, insula, middle temporal gyrus, thalami, both superior temporal gyri decreased in the CM group. In the IEM group, the changes of function focus on the regions associated with coding, conduction and regulation of pain signals. In the FEM group, functional alterations mainly concentrated on the regions associated with pain regulation and emotion cognition. In the CM group, the changes focus on the regions related to spatial attention and cognition, affective disorders and pain feedback, which may be associated with migraine production, development and chronification.


Assuntos
Encéfalo/diagnóstico por imagem , Enxaqueca sem Aura/patologia , Adulto , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
19.
Small ; 14(14): e1704233, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29473308

RESUMO

Hollow nanostructures with mesoporous shells are attractive for their advantageous structure-dependent high-efficiency electrochemical catalytic performances. In this work, a novel nanostructure of Fe-doped CoP hollow triangle plate arrays (Fe-CoP HTPAs) with unique mesoporous shells is designed and synthesized through a room-temperature postsynthetic ligand exchange reaction followed by a facile phosphorization treatment. The mild postsynthetic ligand exchange reaction of the presynthesized ZIF-67 TPAs with K4 [Fe(CN)6 ] in an aqueous solution at room temperature is of critical importance in achieving the final hollow nanostructure, which results in the production of CoFe(II)-PBA HTPAs that not only determine the formation of the interior voids in the nanostructure, but also provide the doping of Fe atoms to the CoP lattice. As expected, the as-prepared mesoporous Fe-CoP HTPAs exhibit pronounced activity for water splitting owing to the advantages of abundant active reaction sites, short electron and ion pathways, and favorable hydrogen adsorption free energy (ΔGH* ). For the hydrogen and oxygen evolution reactions with the Fe-CoP HTPAs in alkaline medium, the low overpotentials of 98 and 230 mV are observed, respectively, and the required cell voltage toward overall water splitting is only as low as 1.59 V for the driving current density of 10 mA cm-2 .

20.
Exp Cell Res ; 331(2): 369-76, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25576386

RESUMO

Nodal modulator 1 (NOMO1), a highly conserved transmembrane protein, has been identified as a part of a protein complex that participates in the Nodal signaling pathway, a critical determinant of heart and visceral organ formation. We previously found that the NOMO1 gene was substantially downregulated in human ventricular septal defect (VSD) myocardium and, thus, may be an important molecular pathway in human heart development. In this study, we aimed to investigate the effects of NOMO1 gene silencing by RNA interference (RNAi) during early mouse cardiac differentiation using P19 cells as a model system. Our results revealed that the differentiated P19 cell population exhibited downregulated NOMO1 levels and expressed lower levels of Nodal signaling mediators, such as Nodal, Cripto and Smad2, than the negative control. Similarly, cardiomyocyte-specific sarcomeric markers, such as cardiac troponin T, as well as expression of cardiogenesis-related transcriptional factors, such as Nkx2.5, Gata4 and Tbx5 were found to be downregulated in P19 differentiated cardiomyocytes in NOMO1-silenced cells when compared to controls. In conclusion, our results indicate that NOMO1 gene knockdown inhibits the differentiation of P19 cells into cardiomyocytes, which highlights a potential role for NOMO1 in early cardiogenesis.


Assuntos
Diferenciação Celular/genética , Coração/embriologia , Miócitos Cardíacos/citologia , Proteína Nodal/genética , Animais , Linhagem Celular , Regulação para Baixo , Fator de Crescimento Epidérmico/biossíntese , Fator de Crescimento Epidérmico/genética , Fator de Transcrição GATA4/biossíntese , Fator de Transcrição GATA4/genética , Comunicação Interventricular/genética , Proteína Homeobox Nkx-2.5 , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Camundongos , Miócitos Cardíacos/metabolismo , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Interferente Pequeno , Transdução de Sinais/genética , Proteína Smad2/biossíntese , Proteína Smad2/genética , Proteínas com Domínio T/biossíntese , Proteínas com Domínio T/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Troponina T/biossíntese , Troponina T/genética
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