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1.
Mater Sci Eng C Mater Biol Appl ; 128: 112272, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474831

RESUMO

Integrating multiple materials with different functionalities in a single nanostructure enables advances in many scientific and technological applications. However, such highly sophisticated nanomaterials usually require complex synthesis processes that complicate their preparation in a sustainable and industrially feasible manner. Herein, we designed a simple general method to grow a mesoporous silica shell onto any combination of hydrophilic nanoparticle cores. The synthetic strategy, based on the adjustment of the key parameters of the sol-gel process for the silica shell formation, allows for the embedment of single, double, and triple inorganic nanoparticles within the same shell, as well as the size-control of the obtained nanocomposites. No additional interfacial adhesive layer is required on the nanoparticle surfaces for the embedding process. Adopting this approach, electrostatically stabilized, small-sized (from 4 to 15 nm) CeO2, Fe3O4, Gd2O3, NaYF4, Au, and Ag cores were used to test the methodology. The mean diameter of the resulting nanocomposites could be as low as 55 nm, with high monodispersity. These are very feasible sizes for biological intervention, and we further observed increased nanoparticle stability in physiological environments. As a demonstration of their increased activity as a result of this, the antioxidant activity of CeO2 cores was enhanced when in core-shell form. Remarkably, the method is conducted entirely at room temperature, atmospheric conditions, and in aqueous solvent with the use of ethanol as co-solvent. These facile and even "green" synthesis conditions favor scalability and easy preparation of multicomponent nanocomposite libraries with standard laboratory glassware and simple benchtop chemistry, through this sustainable and cost-effective fabrication process.


Assuntos
Nanocompostos , Nanopartículas , Dióxido de Silício
2.
Theranostics ; 11(16): 8112-8128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335983

RESUMO

The coiled-coil domain containing protein members have been well documented for their roles in many diseases including cancers. However, the function of the coiled-coil domain containing 65 (CCDC65) remains unknown in tumorigenesis including gastric cancer. Methods: CCDC65 expression and its correlation with clinical features and prognosis of gastric cancer were analyzed in tissue. The biological role and molecular basis of CCDC65 were performed via in vitro and in vivo assays and a various of experimental methods including co-immunoprecipitation (Co-IP), GST-pull down and ubiquitination analysis et al. Finally, whether metformin affects the pathogenesis of gastric cancer by regulating CCDC65 and its-mediated signaling was investigated. Results: Here, we found that downregulated CCDC65 level was showed as an unfavourable factor in gastric cancer patients. Subsequently, CCDC65 or its domain (a.a. 130-484) was identified as a significant suppressor in GC growth and metastasis in vitro and in vivo. Molecular basis showed that CCDC65 bound to ENO1, an oncogenic factor has been widely reported to promote the tumor pathogenesis, by its domain (a.a. 130-484) and further promoted ubiquitylation and degradation of ENO1 by recruiting E3 ubiquitin ligase FBXW7. The downregulated ENO1 decreased the binding with AKT1 and further inactivated AKT1, which led to the loss of cell proliferation and EMT signal. Finally, we observed that metformin, a new anti-cancer drug, can significantly induce CCDC65 to suppress ENO1-AKT1 complex-mediated cell proliferation and EMT signals and finally suppresses the malignant phenotypes of gastric cancer cells. Conclusion: These results firstly highlight a critical role of CCDC65 in suppressing ENO1-AKT1 pathway to reduce the progression of gastric cancer and reveals a new molecular mechanism for metformin in suppressing gastric cancer. Our present study provides a new insight into the mechanism and therapy for gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Glicoproteínas/metabolismo , Fosfopiruvato Hidratase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , China , Feminino , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Glicoproteínas/genética , Humanos , Masculino , Metformina/metabolismo , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oncogenes , Prognóstico , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
3.
Artigo em Inglês | MEDLINE | ID: mdl-33669684

RESUMO

Seepage plays a key role in nutrient loss and easily occurs in widely-used contour ridge systems due to the ponding process. However, the characteristics of nutrient loss and its influential factors under seepage with rainfall condition in contour ridge systems are still unclear. In this study, 23 seepage and rainfall simulation experiments are arranged in an orthogonal rotatable central composite design to investigate the role of ridge height, row grade, and field slope on Nitrate (NO3--N) and Orthophosphate (PO4+3-P) losses resulting from seepage in contour ridge systems. In total, three types of NO3--N and PO4+3-P loss were observed according to erosion processes of inter-rill-headward, inter-rill-headward-contour failure, and inter-rill-headward-contour failure-rill. Our results demonstrated that second-order polynomial regression models were obtained to predict NO3--N and PO4+3-P loss with the independent variables of ridge height, row grade, and field slope. Ridge height was the most important factor for nutrient loss, with a significantly positive effect and the greatest contribution (52.35-53.47%). The secondary factor of row grade exerted a significant and negative effect, and was with a contribution of 19.86-24.11% to nutrient loss. The interaction between ridge height and row grade revealed a significantly negative effect on NO3--N loss, whereas interactions among the three factors did not significantly affect PO4+3-P loss. Field slope only significantly affected NO3--N loss. The optimal design of a contour ridge system to control nutrient loss was obtained at ridge height of 8 cm, row grade of 2°, and field slope of 6.5°. This study provides a method to assess and model nutrient loss, and improves guidance to implement contour ridge systems in terms of nutrient loss control.


Assuntos
Nitratos , Fosfatos , Nutrientes , Fósforo , Chuva , Solo , Movimentos da Água
4.
Mol Ther Nucleic Acids ; 22: 572-583, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230458

RESUMO

Aberrant activation of nuclear factor κB (NF-κB)/RELA is often found in lung adenocarcinoma (LUAD). In this study, we determined that microRNA-3613-5p (miR-3613-5p) plays a crucial role in RELA-mediated post-transcriptional regulation of LUAD cell proliferation. Expression of miR-3613-5p in clinical LUAD specimens is associated with poor prognosis in LUAD. Upregulation of miR-3613-5p promotes LUAD cell proliferation in vitro and in vivo. Our results suggested a mechanism whereby miR-3613-5p expression is induced by RELA through its direct interaction with JUN, thereby stimulating the AKT/mitogen-activated protein kinase (MAPK) pathway by directly targeting NR5A2. In addition, we also found that phosphorylation of AKT1 and MAPK3/1 co-transactivates RELA, thus constituting a RELA/JUN/miR-3613-5p/NR5A2/AKT1/MAPK3/1 positive feedback loop, leading to persistent NF-κB activation. Our findings also revealed that miR-3613-5p plays an oncogenic role in LUAD by promoting cell proliferation and acting as a key regulator of the positive feedback loop underlying the link between the NF-κB/RELA and AKT/MAPK pathways.

5.
Cancer Cell Int ; 20: 502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061854

RESUMO

Background: Non-small cell lung cancer (NSCLC) includes lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MicroRNA (miRNA) plays an important role in the regulation of post-transcriptional gene expression in animals and plants, especially in lung adenocarcinoma. Methods: MiR-1307-5p is an miRNA with significant differences screened by the second generation of high-throughput sequencing in the early stage of our research group. In the current study, a series of in vitro and in vivo experiments were carried out. MiR-1307-5p mimic, miR-1307-5p inhibitor, and NC were transfected into A549 and H1299 lung adenocarcinoma cells. The correlation between miR-1307-5p and clinicopathological features in pathological samples was analyzed using a lung adenocarcinoma tissue microarray, and miR-1307-5p expression was detected by qPCR. CCK-8, EdU, colony formation, scratch test, and Transwell assays were used to observe cell proliferation and migration. Double luciferase assay, western blot, qPCR, and immunohistochemistry were employed in confirming the target relationship between miR-1307-5p and TRAF3. Western blotting was used to analyze the relationship between miR-1307-5p and the NF-κB/MAPK pathway. Finally, the effect of miR-1307-5p on tumor growth was studied using a subcutaneous tumorigenesis model in nude mice. Results: Increased miR-1307-5p expression was significantly related to decreased overall survival rate of lung adenocarcinoma patients, revealing miR-1307-5p as a potential oncogene in lung adenocarcinoma. MiR-1307-5p mimic significantly promoted while miR-1307-5p inhibitor reduced the growth and proliferation of A549 and H1299 cells. MiR-1307-5p overexpression significantly enhanced the migration ability while miR-1307-5p inhibition reduced the migration ability of A549 and H1299 cells. Target binding of miR-1307-5p to TRAF3 was confirmed by double luciferase assay, western blot, qPCR, and immunohistochemistry. miR-1307-5p caused degradation of TRAF3 mRNA and protein. MiR-1307-5p targeted TRAF3 and activated the NF-κB/MAPK pathway. TRAF3 colocalized with p65 and the localization of TRAF3 and p65 changed in each treatment group. Tumor volume of the lv-miR-1307-5p group was significantly larger than that of the lv-NC group, and that of the lv-miR-1307-5p-inhibitor group was significantly smaller than that of the lv-NC group. Conclusion: In conclusion, miR-1307-5p targets TRAF3 and activates the NF-κB/MAPK pathway to promote proliferation in lung adenocarcinoma.

6.
Biomaterials ; 255: 120197, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32563944

RESUMO

Bone endoprosthesis in patients with systemic chronic inflammation frequently leads to poor osseointegration after implantation mainly due to the increase in pro-inflammatory cytokines that induce bone resorption and impair bone formation. In this work, peptide-coated implants are designed to create a beneficial bone immune microenvironment around prostheses to promote interfacial osteogenesis. By taking advantage of the spontaneous and stable coordination chemistry, Ti-based implants are coated with the mussel-inspired peptide to mitigate lipopolysaccharide (LPS)-induced inflammation by up-regulating the M2 phenotype of macrophages. In addition, the peptide coating increases the bone-implant contact (BIC) by nearly 3 times resulting in suppressed osteoclastogenesis and promoted osteogenesis by inhibiting the nuclear factor kappa-B (NF-κB) signalling pathway. Our findings indicate that biomimetic peptides with osteoimmunomodulatory bioactivity can be incorporated into Ti-based prostheses to facilitate bone regeneration in patients with chronic inflammatory diseases.


Assuntos
Osseointegração , Osteogênese , Biomimética , Materiais Revestidos Biocompatíveis , Humanos , Inflamação , Peptídeos , Propriedades de Superfície , Titânio
7.
ACS Nano ; 14(6): 7259-7268, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32433868

RESUMO

Room-temperature sodium-sulfur (RT-Na/S) batteries hold great promise for sustainable and cost-effective applications. Nevertheless, it remains a great challenge to achieve high capacity and cycling stability due to the low activity of sulfur and the sluggish conversion kinetics between polysulfide intermediates and sodium sulfide. Herein, an electrocatalyzing S cathode is fabricated, which consists of porous core-shell structure and multisulfiphilic sites. The flexible carbon structure effectively buffers volume changes during cycling and provides enclosed spaces to store S8 with exceptional conductivity. Significantly, the multisulfiphilic sites (ZnS and CoS2) enhance catalysis toward multistep S conversion, which effectively suppresses long-chain polysulfides dissolution and improves the kinetics of short-chain polysulfides. Thus, the obtained S cathodes achieve an enhanced cycling performance (570 mAh g-1 at 0.2 A g-1 over 1000 cycles), decent rate capability (250 mAh g-1 at 1.0 A g-1 over 2000 cycles), and high energy density of 384 Wh kg-1 toward practical applications.

8.
Neurochem Res ; 45(5): 1034-1044, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32016793

RESUMO

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Induction of endogenous antioxidants to act against oxidative stress-mediated neuronal damage seems to be a reasonable strategy for delaying the progression of such diseases. In this study, we investigated the neuroprotective effect of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells and the possible signaling pathways involved. The differentiated PC12 cell line was pretreated with DDW containing different concentrations (50-100 ppm) of deuterium and then treated with H2O2 to induce oxidative stress and neurotoxicity. We assessed cell survival, reactive oxygen species (ROS) generation, TUNEL assay, catalase (CAT), copper and zinc-containing superoxide dismutase (CuZn-SOD) and superoxide dismutase (SOD) activity and performed Western blot analysis to investigate the neuroprotective effect of DDW. The results indicated that DDW could attenuate H2O2-induced apoptosis, reduce ROS formation, and increase CAT, CuZn-SOD and SOD activity in H2O2-treated PC12 cells. Western blot analysis revealed that DDW treatment significantly increased the expression of p-Akt, Bcl-2 and GSK-3ß. However, the protective effect of DDW on cell survival and the DDW-mediated increases in p-Akt, Bcl-2 and GSK-3ß were abolished by pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In summary, DDW may protect differentiated PC12 cells against H2O2-induced oxidative stress through the PI3K/Akt signaling pathway.


Assuntos
Deutério/administração & dosagem , Peróxido de Hidrogênio/toxicidade , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Água/administração & dosagem , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Estresse Oxidativo/fisiologia , Células PC12 , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
9.
Int J Geriatr Psychiatry ; 35(5): 537-546, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31994767

RESUMO

OBJECTIVES: We aimed to analyze the effects of multidomain attention training on alertness, sustained attention, and visual-spatial attention in older adults with mild cognitive impairment (MCI). DESIGN: The design used in this study was a two-arm, parallel group, double-blind randomized controlled trial. SETTING AND PARTICIPANTS: The participants of the study were seventy-eight older adults with MCI (mean age: 79.5 ± 7.9 years) from retirement centers and community housing for the elderly. INTERVENTION: The participants were randomly assigned to an experimental group (multidomain attention training, n = 39) or an active control group (n = 39). Both groups underwent training sessions for 45 minutes three times per week for 6 weeks (18 sessions in total). MEASURES: The main efficacy indicator was alertness (Trail Making Test Part B), sustained attention (Digit Vigilance Test), and visual-spatial attention (Trail Making Test Part A). The secondary outcome indicators were other cognitive functions (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA] subscales). Measurements were obtained at pretest, posttest, and 3 and 6 months after training. RESULTS: The results were analyzed by a generalized estimating equation (GEE), which indicated that attention outcomes (alertness, sustained attention, and visual-spatial attention) of the experimental group did not improve after training. However, the experimental group displayed a significant improvement in the attention, memory, and orientation of MMSE and MoCA subscales over a period of 6 months and also showed superior results compared with the control group. CONCLUSIONS: Multidomain attention training demonstrated improved alertness and visual-spatial attention for posttest after 6 months. We also outline potential future advances in attention training for improving attention in older adults with MCI.


Assuntos
Atenção/fisiologia , Cognição/fisiologia , Terapia Cognitivo-Comportamental/métodos , Disfunção Cognitiva/terapia , Função Executiva/fisiologia , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Memória , Testes de Estado Mental e Demência , Teste de Sequência Alfanumérica , Resultado do Tratamento
10.
Cell Rep ; 28(6): 1400-1409.e4, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31390555

RESUMO

A multitude of signals are coordinated to maintain self-renewal in embryonic stem cells (ESCs). To unravel the essential internal and external signals required for sustaining the ESC state, we expand upon a set of ESC pluripotency-associated phosphoregulators (PRs) identified previously by short hairpin RNA (shRNA) screening. In addition to the previously described Aurka, we identify 4 additional PRs (Bub1b, Chek1, Ppm1g, and Ppp2r1b) whose depletion compromises self-renewal and leads to consequent differentiation. Global gene expression profiling and computational analyses reveal that knockdown of the 5 PRs leads to DNA damage/genome instability, activating p53 and culminating in ESC differentiation. Similarly, depletion of genome integrity-associated genes involved in DNA replication and checkpoint, mRNA processing, and Charcot-Marie-Tooth disease lead to compromise of ESC self-renewal via an increase in p53 activity. Our studies demonstrate an essential link between genomic integrity and developmental cell fate regulation in ESCs.


Assuntos
Diferenciação Celular/genética , Células-Tronco Embrionárias/fisiologia , Instabilidade Genômica , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/fisiologia , Linhagem Celular , Dano ao DNA , Perfilação da Expressão Gênica , Teste de Complementação Genética , Camundongos , Fosfoproteínas/genética , Fosfoproteínas/fisiologia , RNA Interferente Pequeno , Transdução de Sinais , Proteína Supressora de Tumor p53/fisiologia
11.
Virology ; 536: 49-57, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400549

RESUMO

Molecular adjuvants are vaccine delivery vehicle to increase specific antigens effectiveness. Herein, we concentrated on IgG Fc, an effective molecular adjuvant, to develop novel pseudorabies virus (PRV) subunit vaccines. Two major protective antigen genes of PRV were constructed and linked into the mouse IgG Fc fragment. The gD, gD-IgG2aFc, gB and gB-IgG2aFc proteins were expressed using a baculovirus system. Mice intranasally immunized with gD-IgG2aFc or gB-IgG2aFc subunit vaccine exhibited significantly higher PRV-specific antibodies, neutralizing antibodies and intracellular cytokines than the mice intranasally immunized with gD or gB subunit vaccine. Moreover, no histopathological lesions were observed in mice immunized with gB-IgG2aFc subunit vaccine via histopathology examination. Further, the gB-IgG2aFc subunit vaccine was efficient for PRV infection compared with live attenuated vaccine. Overall, these results suggest that IgG2a Fc fragment, as a potential molecular adjuvant, fused with PRV antigen might be a promising and efficient PRV vaccine candidate.


Assuntos
Herpesvirus Suídeo 1/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/biossíntese , Vacinas contra Pseudorraiva/biossíntese , Pseudorraiva/prevenção & controle , Proteínas Recombinantes de Fusão/biossíntese , Proteínas do Envelope Viral/biossíntese , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/biossíntese , Adjuvantes Imunológicos/genética , Animais , Anticorpos Antivirais/biossíntese , Baculoviridae/genética , Baculoviridae/metabolismo , Citocinas/genética , Citocinas/imunologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Glicoproteínas/administração & dosagem , Glicoproteínas/biossíntese , Glicoproteínas/genética , Herpesvirus Suídeo 1/genética , Herpesvirus Suídeo 1/imunologia , Herpesvirus Suídeo 1/patogenicidade , Imunização , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/administração & dosagem , Imunoglobulina G/biossíntese , Imunoglobulina G/genética , Rim/patologia , Rim/virologia , Camundongos , Camundongos Endogâmicos BALB C , Pseudorraiva/imunologia , Pseudorraiva/mortalidade , Pseudorraiva/virologia , Vacinas contra Pseudorraiva/administração & dosagem , Vacinas contra Pseudorraiva/genética , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Análise de Sobrevida , Suínos , Vacinas de Subunidades , Proteínas do Envelope Viral/administração & dosagem , Proteínas do Envelope Viral/genética
12.
Am J Geriatr Psychiatry ; 27(11): 1257-1267, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31248769

RESUMO

OBJECTIVES: To examine the immediate and long-term effects of executive attention training on selective attention, focused attention, and divided attention in older adults with mild cognitive impairment. METHODS: A double-blind, multisite randomized controlled trial at five sites. Seventy participants (mean age: 78.19 ± 7.22 years) were assigned to an experimental group (executive attention training, n = 35) or an active control group (n = 35). The training duration was the same for both groups (45 minutes per session, 3 times per week, 18 sessions in total). Primary outcome measure was selective attention (Digit Span Task). Secondary outcome measures included focused attention (Stroop Color Word Test) and divided attention (Trail-Making Test Part B). Data were collected at pretest, post-test, 3-month follow-up, and 6-month follow-up. RESULTS: In GEE analysis, findings indicated a significant improvement in selective attention at post-test, whereas divided attention showed significant reducing omission error at 3-month follow-up. There was no significant effect of group in focused attention associated with the executive attention training compared with active control group. CONCLUSION: The executive attention training significantly improved selective attention and divided attention performance. Future studies should identify transfer effects of attention training, and that can employ early screening to provide integrated attention training, and decrease its relevant risks on competency in performing daily activities, such as falling and driving.


Assuntos
Atenção , Terapia Cognitivo-Comportamental/métodos , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/reabilitação , Função Executiva , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Tempo de Reação , Taiwan
13.
Hu Li Za Zhi ; 66(3): 92-99, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31134604

RESUMO

BACKGROUND & PROBLEMS: Clinical ladder (CL)-3 nurses should have both an ability to integrate the clinical information of critically ill patients and to carry out the administrative work of the intensive care unit. However, in our unit, only 15.3% of nurses hold CL-3 certification, which is much lower than the hospital average of 23.1%. Thus, we initiated a project to raise this percentage in our unit. An analysis in January 2016 showed that the main obstacles to obtaining CL-3 certification in our unit were inability to write case reports, inadequate in-service education, and a lack of certified educators. PURPOSE: The purpose of this project was to increase the number of CL-3-certified nurses in our intensive care unit. RESOLUTION: The resolution included holding courses on case report writing, briefings, and oral presentation techniques; assigning a preceptor to make nursing staff assignments; encouraging nurses to participate in the clinical nursing preceptor education training camp; and conducting practice tests using a multiple assessment tool. RESULTS: After implementation of this project, the percentage of unit nurses who had passed CL-3 increased to 39.0%. CONCLUSIONS: This project not only allowed our fellow nurses to share in the joy of clinical ladder advancement but also improved the atmosphere in the unit by encouraging self-development. This project helped stimulate professional growth among our staff and improved the quality of clinical care.


Assuntos
Certificação/estatística & dados numéricos , Unidades de Terapia Intensiva , Recursos Humanos de Enfermagem no Hospital , Mobilidade Ocupacional , Educação em Enfermagem , Humanos
14.
Am J Cancer Res ; 9(3): 479-495, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949405

RESUMO

Nasopharyngeal carcinoma (NPC), arising from the nasopharynx epithelium, is prevalent among South and East Asia. The radiotherapy is the primary treatment for NPC patients. However, the acquired radioresistance dramatically diminishes the therapeutic effect of radiotherapy. Meanwhile, recurrence and metastasis always occur in line with the radioresistance, but the underlying mechanisms are still unclear. In this study, we established two radioresistant NPC cell lines, CNE1R and SUNE1R, by sequentially irradiated parental CNE1 and SUNE1 cells up to a clinical treatment dose of 72 Gy. A transcriptome profile analysis of CNE1R and CNE1 reveals that activated oncogenic pathways are highly enriched in CNE1R. As the result, CNE1R showed higher proliferation rate but lower apoptosis rate after irradiation, and enhanced metastasis ability in comparison with CNE1. Significantly, a group of metastasis associated genes were increased in CNE1R while the irradiation proceeded, including several matrix metallopeptidase (MMP) members, especially MMP10 and MMP13. With further analysis, we found both MMP10 and MMP13 are highly upregulated in metastatic head and neck cancer specimens compared to non-metastatic ones. More importantly, patients with lower expression of both MMP10 and MMP13 showed a better five-year survival than the double high group. Our findings unveiled the potential mechanisms of radioresistance related metastasis in NPC patients, and the increase of MMP10 and MMP13 may serve as high risk factors for metastasis during radiotherapy.

15.
Age Ageing ; 48(4): 519-525, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30989165

RESUMO

BACKGROUND: memory training is a potential intervention for retaining memory and reducing dementia risk in older adults with mild cognitive impairment (MCI). OBJECTIVE: this study examined the effect of virtual interactive working memory training (VIMT) in older adults with MCI. DESIGN: single-blind, two-arm parallel-group, randomised controlled design. SETTING: retirement homes, institutions, and communities. SUBJECTS: a total of 66 older adults with MCI were recruited (mean age: 78.5 ± 7.6 years). METHODS: participants were randomly assigned to the experimental group (VIMT, n = 33) or active control group (n = 33). The VIMT program used the CogniPlus (includes four training modules). Both groups attended 45 min sessions 3 times per week, a total of 36 sessions. The primary outcome was working memory; secondary outcomes were immediate memory, delayed memory, subjective memory complaints and global cognitive function. All variables were measured at pre-test, post-test, and 3-month follow-up. RESULTS: between group, the effect of working memory adjusted mean difference by 1.75 (95% CI: 0.56 to 2.94; P < 0.01) at post-test. The results were analysed by a generalised estimating equation, which indicated that VIMT group significantly improved working memory at post-test (P = 0.01) relative to the active control group. CONCLUSIONS: the applied VIMT program can enable older adults with MCI to maintain their working memory and reduce the rate of cognitive deterioration. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov (no.: NCT02462135).


Assuntos
Disfunção Cognitiva/terapia , Aprendizagem , Memória de Curto Prazo , Interface Usuário-Computador , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Método Simples-Cego
16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(2): 214-220, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30827312

RESUMO

OBJECTIVE: To systematically analyze the effect of haemoperfusion (HP) combined with continuous veno-veno haemofiltration (CVVH) in the treatment of the patients with paraquat poisoning (PQP). METHODS: Words of paraquat, poisoning, continuous venous hemofiltration, hemoperfusion, hemodiafiltration in Chinese and paraquat, poisoning, intoxication, haemofiltration, continuous venovenous haemofiltration, haemoperfusion in English were chosen as keywords, the Chinese and English literatures about acute PQP treated with HP combined with CVVH published in Wanfang database, CNKI, CBM, VIP database, PubMed, Embase, Cochrane Library were searched by computer, and the retrieval time was from the establishment of the database to July 2018. The experimental group was treated with HP combined with CVVH, while the control group was treated with HP alone. Besides, the outcome indicators included mortality, survival time of dead patients (the patient's time from exposure to poison to death), serum creatinine (SCr), alanine aminotransferase (ALT), arterial partial pressure of oxygen (PaO2), and incidence of circulatory and respiratory failure. The literature data were extracted by two researchers independently, the quality of the literature was evaluated according to the modified Jadad score table or Newcastle-Ottawa scale (NOS), and the Meta-analysis was carried out by RevMan 5.3 software; and the stability of the results of Meta-analysis was tested by sensitivity analysis. Further, the publication bias was analyzed through drawing a funnel diagram. RESULTS: Finally, 20 articles were included, with 18 in Chinese and 2 in English. Among them, 6 were randomized controlled trial (RCT) and 14 were case-control studies. Furthermore, a total of 2 870 patients were involved, with 1 558 in the control group and 1 312 in the experimental group. Meta-analysis showed that the mortality rate of patients in the experimental group was significantly lower than that in the control group [odds ratio (OR) = 0.55, 95% confidence interval (95%CI) = 0.42 to 0.73, P < 0.000 1], the patients' time from toxin exposure to death was significantly longer than that in the control group [standard mean difference (SMD) = 2.16, 95%CI = 1.46 to 2.86, P < 0.000 01). In the course of treatment, the peak value of SCr in the experimental group was significantly lower than that in the control group (SMD = -0.53, 95%CI = -0.65 to -0.42, P < 0.000 01), and the peak value of ALT was also decreased (SMD = -0.72, 95%CI = -0.99 to -0.44, P < 0.000 01). Besides, there was no significant difference in PaO2 between the two groups on the 3rd day of treatment (SMD = 0.15, 95%CI = -0.19-0.49, P = 0.40), but on the 7th day, PaO2 in the experimental group was significantly higher than that in the control group (SMD = 0.23, 95%CI = 0.29 to 0.98, P = 0.000 3). Furthermore, the incidence of circulatory failure in the experimental group was significantly lower than that in the control group (OR = 0.26, 95%CI = 0.19 to 0.37, P < 0.000 01), but the incidence of respiratory failure was significantly higher than that in the control group (OR = 4.14, 95%CI = 3.00 to 5.72, P < 0.000 01). The influence of heterogeneity on statistical results was excluded in the sensitivity analysis, and funnel plot diagram was applied to indicate the publication bias of mortality and survival time of the dead patients. CONCLUSIONS: Combined with HP alone, HP combined with CVVH could better improve liver and kidney function and oxygenation state of PQP patients, reduce the incidence of early circulatory failure, prolong the survival time and reduce the death rate of PQP patients.


Assuntos
Hemofiltração/métodos , Hemoperfusão/métodos , Paraquat/envenenamento , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(1): 44-49, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30707868

RESUMO

OBJECTIVE: To compare the influence of sevoflurane inhalation sedation and propofol intravenous sedation on duration of endotracheal intubation as well as the length of intensive care unit (ICU) stay and total length of hospital stay in postoperative critical patients. METHODS: Six databases including CNKI, Wanfang data, PubMed, Embase, Cochrane Library and Web of Science were searched for randomized controlled trials (RCTs) about the influence of sevoflurane inhalation sedation or propofol intravenous sedation on the sedation time, the duration of endotracheal intubation, the length of ICU stay, the total length of hospital stay and the adverse effects rate in postoperative critical patients from the time of database establishment to July 2018. At the same time, the reference materials of included literature were retrieved manually. All literatures were screened by three independent reviewers, and the data extraction and quality evaluation of the included studies were conducted. Meta-analysis was used for RCT that met the quality standards. RESULTS: A total of 7 RCT studies were enrolled involving 537 patients who were all transferred into ICU after surgery with trachea cannula. Among the patients, 272 received sevoflurane sedation while the other 265 received propofol sedation. All the included studies were well designed and of high quality. The results of Meta-analysis showed that compared with propofol sedation, sevoflurane sedation could significantly shorten the duration of endotracheal intubation [standardized mean difference (SMD) = -0.60, 95% confidence interval (95%CI) = -0.88 to -0.31, P < 0.000 1] and the total length of hospital stay (SMD = -0.36, 95%CI = -0.61 to -0.12, P = 0.003), and lower the cardiac troponin T (cTnT) within 12-24 hours after ICU admission (SMD = -0.61, 95%CI = -0.85 to -0.36, P < 0.000 01). There was no significant difference in the sedation time (SMD = -0.07, 95%CI = -0.29 to 0.15, P = 0.52), the length of ICU stay (SMD = -0.19, 95%CI = -0.39 to 0.01, P = 0.06), the incidence of nausea and vomiting [odds ratio (OR) = 1.19, 95%CI = 0.61 to 2.32, P = 0.61] or incidence of delirium (OR = 0.80, 95%CI = 0.34 to 1.90, P = 0.62) between sevoflurane group and propofol group. CONCLUSIONS: Sevoflurane inhalation sedation may lead to shorter duration of endotracheal intubation and total length of hospital stay, and had better protection for myocardium as compared with propofol intravenous sedation. The above conclusions needed further study to confirm, due to the lack of literature enrolled in this Meta-analysis.


Assuntos
Anestésicos Inalatórios , Intubação Intratraqueal/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Sevoflurano/administração & dosagem , Anestésicos Intravenosos , Cuidados Críticos , Humanos , Propofol/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Operatórios
18.
J Agric Food Chem ; 66(43): 11337-11346, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30301351

RESUMO

Saponins, the primary phytochemicals contributing to the health properties of G. pentaphyllum were frequently studied. However, compounds responsible for its bioactivities were still poorly understood. The saponin-rich fraction (GPMS), 3- O-[2G-( E)-Coumaroyl-3G- O-ß-d-glucosyl-3R- O-ß-d-glucosylrutinoside] (KCGG), gypenoside XLVI and gypenoside L were obtained by purification of G. pentaphyllum. The compounds were examined and compared with GPMS for their inhibitory effects on LPS-induced nitric oxide (NO) production. GPMS and KCGG differed in their inhibitory capacities against pro-inflammatory cytokines secretion. GPMS exhibited strong inhibition on inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) mRNA expression but weak inhibition on tumor necrosis factor-α (TNF-α) and interleukin-1ß mRNA expression. KCGG was better at inhibiting iNOS, IL-6, TNF-α, and cyclooxygenase-2 (COX-2) mRNA expression. GPMS showed similar inhibitory potency on mitogen-activated protein kinase phosphorylation and nuclear factor-κB (NF-κB) activation, as evidenced by their regulatory effects on LPS-induced P65 phosphorylation, NF-κB nuclear translocation, IκBα phosphorylation and degradation, IκKα/ß phosphorylation, c-Jun N-terminal kinase phosphorylation, P38 phosphorylation, and COX-2 expression. KCGG was more powerful in inhibiting the NF-κB pathway, suggesting that KCGG might be used in the management of inflammatory-associated diseases in which NF-κB played pivotal roles. Furthermore, KCGG might be mainly responsible for the predominant effects of GPMS.


Assuntos
Anti-Infecciosos/farmacologia , Gynostemma/química , Macrófagos/efeitos dos fármacos , Saponinas/farmacologia , Animais , Citocinas/metabolismo , Glucosídeos/farmacologia , Inflamação , Lipopolissacarídeos , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/farmacologia , Células RAW 264.7
19.
Oncol Rep ; 40(5): 2536-2546, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226609

RESUMO

Distant metastasis is the major contributor to treatment failure and mortality in patients with nasopharyngeal carcinoma (NPC). The lack of effective treatment strategies for metastatic NPC is the major cause for the low survival rate. Therefore, it is crucial to understand the molecular mechanisms underlying NPC metastasis and to identify potential biomarkers for targeted therapy. MicroRNA (miRNAs or miRs) have been shown to play an important role in tumorigenesis and metastasis. In the present study, we aimed to evaluate the significance of hsa­miR­24 in NPC metastasis. Significantly lower hsa­miR­24 levels were observed in NPC metastatic tumors and higher hsa­miR­24 levels were associated with longer progression­free and metastasis­free survival durations. hsa­miR­24 overexpression inhibited cell proliferation, invasion and migration. Using bioinformatics approaches together with functional luciferase reporter assays, we demonstrated that the c­Myc 3'­UTR was a direct target of hsa­miR­24 in regulating NPC metastasis. Protein profiling analysis revealed that a high c­Myc expression was inversely associated with metastasis­free overall survival and with epithelial­mesenchymal transition (EMT). Furthermore, the overexpression of hsa­miR­24 decreased NPC cell invasive ability induced by the overexpression of c­Myc, associated with EMT epithelial marker (E­cadherin) restoration. Thus, on the whole, the findings of this study demonstrate that hsa­miR­24 suppresses metastasis in NPC by regulating the c­Myc/EMT axis, suggesting that hsa­miR­24 may be used as a prognostic factor and as a novel target for the prevention of NPC metastasis.


Assuntos
Carcinoma/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Proteínas Proto-Oncogênicas c-myc/genética , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Transdução de Sinais/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-29866875

RESUMO

Delivery of pharmacologically active nucleoside triphosphate analogs to sites of viral infection is challenging. In prior work we identified a 2'-C-methyl-1'-cyano-7-deaza-adenosine C-nucleotide analog with desirable selectivity and potency for the treatment of hepatitis C virus (HCV) infection. However, the prodrug selected for clinical development, GS-6620, required a high dose for meaningful efficacy and had unacceptable variability due to poor oral absorption as a result of suboptimal solubility, intestinal metabolism, and efflux transport. While obtaining clinical proof of concept for the nucleotide analog, a more effective prodrug strategy would be necessary for clinical utility. Here, we report an alternative prodrug of the same nucleoside analog identified to address liabilities of GS-6620. A phosphoramidate prodrug containing the nonproteinogenic amino acid methylalanine, an isopropyl ester and phenol in the (S) conformation at phosphorous, GS2, was found to have improved solubility, intestinal stability, and hepatic activation. GS2 is a more selective substrate for hepatically expressed carboxyl esterase 1 (CES1) and is resistant to hydrolysis by more widely expressed hydrolases, including cathepsin A (CatA) and CES2. Unlike GS-6620, GS2 was not cleaved by intestinally expressed CES2 and, as a result, was stable in intestinal extracts. Levels of liver triphosphate following oral administration of GS2 in animals were higher than those of GS-6620, even when administered under optimal conditions for GS-6620 absorption. Combined, these properties suggest that GS2 will have better oral absorption in the clinic when administered in a solid dosage form and the potential to extend the clinical proof of concept obtained with GS-6620.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/patogenicidade , Nucleotídeos/uso terapêutico , Pró-Fármacos/uso terapêutico , Triazinas/uso terapêutico , Administração Oral , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Células CACO-2 , Células Cultivadas , Cães , Hepacivirus/efeitos dos fármacos , Hepatite C/virologia , Humanos , Masculino , Nucleotídeos/administração & dosagem , Nucleotídeos/farmacocinética , Pró-Fármacos/administração & dosagem , Pró-Fármacos/farmacocinética , Ratos , Triazinas/administração & dosagem , Triazinas/farmacocinética , Replicação Viral/efeitos dos fármacos
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