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1.
Phys Chem Chem Phys ; 24(40): 24845-24851, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36196615

RESUMO

In this study, X-ray photoelectron spectroscopy is used to analyse nine morpholinium ionic liquids, which are of great interest in green chemistry because of their low toxicity and high recyclability. The effect of the alkyl chain length on the aliphatic C 1s binding energy and the impact of the anion basicity on the cationic N 1s and O 1s binding energies are investigated. It is concluded that by changing the basicity of the anion, there is a more notable change in the electronic environment of the oxygen centre. The impact of a long alkyl side substituent on the cation-anion interactions is also discussed. It is observed that there is an intense charge shielding effect of the alkyl side chain in the cases of octyl and dodecyl substituents, which is reflected in the reduced Br 3d5/2 binding energy.

2.
J Cell Mol Med ; 18(2): 231-41, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24330074

RESUMO

A range of in vitro, experimental and clinical intervention studies have implicated an important role for hyperglycaemia-induced activation of the renin-angiotensin system (RAS) in the development and progression of diabetic nephropathy (DN). Blockade of RAS by angiotensin converting enzyme (ACE) inhibitors is an effective strategy in treating diabetic kidney diseases. However, few studies demonstrate the mechanism by which hyperglycaemia up-regulates the expression of ACE gene. Our previous studies have identified a novel curcumin analogue, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66), which could inhibit the high glucose (HG)-induced phosphorylation of mitogen-activated protein kinases in mouse macrophages. In this study, we found that the renal protection of C66 in diabetic mice was associated with mitogen-activated protein kinase (MAPK) inactivation and ACE/angiotensin II (Ang II) down-regulation. Generally, MAPKs have been considered as a downstream signalling of Ang II and a mediator for Ang II-induced pathophysiological actions. However, using C66 and specific inhibitors as small molecule probes, in vitro experiments demonstrate that the MAPK signalling pathway regulates ACE expression under HG stimulation, which contributes to renal Ang II activation and the development of DN. This study indicates that C66 is a potential candidate of DN therapeutic agents, and more importantly, that reduction in ACE expression by MAPKs inhibition seems to be an alternative strategy for the treatment of DN.


Assuntos
Compostos de Benzilideno/farmacologia , Cicloexanonas/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Hiperglicemia/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/genética , Peptidil Dipeptidase A/genética , Inibidores de Proteínas Quinases/farmacologia , Angiotensina II/genética , Angiotensina II/metabolismo , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Regulação da Expressão Gênica , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/genética , Transdução de Sinais , Estreptozocina
3.
Tumour Biol ; 35(11): 10891-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25085584

RESUMO

The molecular pathway regulating gastric carcinoma (GC) invasiveness and metastasis remains elusive. Here, we detected significant increase in the phosphorylated epidermal growth factor receptor (pEGFR), MMP7, and MMP13 in the resected GC, compared with the adjacent normal tissue, in patients. Moreover, strong positive correlation was detected between pEGFR and MMP7, and between pEGFR and MMP13 in GC. To examine whether a causal link exists, we used two human GC lines, SNU-5 and AGS, to study the cross talk between EGFR signaling activation, and expression of MMP7 and MMP13. We found that EGF-induced EGFR phosphorylation activated both MMP7 and MMP13, and consequently cancer invasiveness. EGF-induced activation of MMP7 and MMP13 can be both inhibited by use of an inhibitor for EGFR. EGF-induced activation of MMP7 can be also significantly inhibited by use of an inhibitor for Akt, but not an inhibitor for ERK1/2, while EGF-induced activation of MMP13 can be significantly inhibited by use of an inhibitor for ERK1/2, but not by an inhibitor for Akt. These data suggest that EGF-induced activation of MMP7 and MMP13 in GC is through phosphatidylinositol 3-kinase (PI3K) and extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway, respectively. Our study thus highlights EGFR signaling regulated MMP7 and MMP13 activation as molecular basis for metastasis of GC, and further demonstrate that different signaling pathway cascades are involved in the downstream signaling transduction.


Assuntos
Movimento Celular , Inibidores Enzimáticos/farmacologia , Receptores ErbB/antagonistas & inibidores , Metaloproteinase 13 da Matriz/química , Metaloproteinase 7 da Matriz/química , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/secundário , Western Blotting , Regulação para Baixo , Fator de Crescimento Epidérmico/farmacologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Células Tumorais Cultivadas
4.
J Chin Med Assoc ; 87(4): 434-441, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38349155

RESUMO

BACKGROUND: In Taiwan, the number of cases of sequential bilateral pediatric cochlear implantation (CI) is increasing but data regarding its effectiveness and impact of the reimbursement policy are lacking. We examined the speech perception and quality of life (QOL) of bilateral prelingually deaf children who underwent sequential CI, considering the effects of age at the time of second implantation and interimplant interval. METHODS: We enrolled 124 Mandarin-speaking participants who underwent initial cochlear implant (CI1) in 2001-2019 and a second CI (CI2) in 2015-2020. Patients were followed up for ≥2 years and were categorized into groups based on age at the time of CI2 implantation (<3.5, 3.6-7, 7.1-10, 10.1-13, and 13.1-18 years) and interimplant interval (0.5-3, 3.1-5, 5.1-7, 7.1-10, and >10 years). We evaluated speech perception, device usage rates, and QOL using subjective questionnaires (Speech, Spatial, and Qualities of Hearing and Comprehension Cochlear Implant Questionnaire). RESULTS: Speech perception scores of CI2 were negatively correlated with ages at the time of CI1 and CI2 implantation and interimplant interval. Older age and a longer interimplant interval were associated with higher nonuse rates for CI2 and worse auditory performance and QOL. Among individuals aged >13 years with interimplant intervals >10 years, up to 44% did not use their second ear. Patients aged 7.1 to 10 years had better speech perception and higher questionnaire scores than those aged 10.1 to 13 and 13.1 to 18 years. Furthermore, patients aged 10.1 to 13 years had a lower rate of continuous CI2 usage compared to those aged 7.1 to 10 years. CONCLUSION: Timely implantation of CI2 is essential to achieve optimal outcomes, particularly among sequentially implanted patients with long-term deafness in the second ear and no improvement with hearing aids following CI1 implantation. For CI2 implantation, an upper limit of age of 10 years and interimplant interval of 7 years are essential to prevent suboptimal outcomes. These data can provide useful information to implant recipients, their families, and medical and audiological professionals, enabling a comprehensive understanding of the benefits and potential impacts of the timing of CI2 implantation.


Assuntos
Implante Coclear , Implantes Cocleares , Humanos , Criança , Qualidade de Vida , Perda Auditiva Bilateral/cirurgia , Resultado do Tratamento
5.
BMC Cancer ; 13: 494, 2013 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-24156374

RESUMO

BACKGROUND: Recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy. METHODS: A bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, the in vivo anti-tumor effect of B82 was evaluated. RESULTS: B82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cells in vitro and inhibited H460 tumor growth in vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress both in vitro and in vivo. CONCLUSIONS: A new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Curcumina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Animais , Antineoplásicos/toxicidade , Antioxidantes/toxicidade , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Curcumina/análogos & derivados , Curcumina/toxicidade , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Camundongos , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Oncol Rep ; 49(5)2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37026529

RESUMO

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that one of the tumor images shown in Fig. 4A was strikingly similar to a tumor image appearing in a pair of other articles that had been written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 2079­2086, 2016; DOI: 10.3892/or.2016.5029].

7.
Front Bioeng Biotechnol ; 11: 1163933, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324441

RESUMO

Introduction: Chronic osteomyelitis remains a clinical challenge in orthopedics. Methods: In this study, silk fibroin microspheres (SFMPs) loaded with vancomycin are entrapped in an injectable silk hydrogel to form a vancomycin delivery system for treatment of chronic osteomyelitis. Results and Discussion: Vancomycin showed continuous release from the hydrogel for up to 25 days. The hydrogel shows strong antibacterial activity against both Escherichia coli and Staphylococcus aureus and a long antibacterial duration of 10 days without a decrease in the antibacterial effect. The injection of vancomycin-loaded silk fibroin microspheres entrapped in the hydrogel into the infected site of rat tibia reduced bone infection and improved bone regeneration compared with other treatment groups. Conclusion: Thus, the composite SF hydrogel features a sustained-release profile and good biocompatibility, making it promising for application in osteomyelitis treatment.

8.
ACS Omega ; 8(34): 30888-30897, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37663496

RESUMO

Photo-cross-linkable hydrogels have recently gained increased interest in the field of biomedical applications. In this study, silk fibroin was derivatized with methacrylic anhydride (MA) to obtain silk fibroin methacryloyl (SFMA), forming hydrogel under UV light exposure in 1 min. The SFMA sol-gel transition did not involve significant structural change at the early stage. Then, the formation of the irreversible ß-sheet was confirmed after 24 h. The resulting SFMA hydrogel showed a homogeneous porous structure with pore sizes ranging from 400 to 700 µm, depending on the content. In addition, these hydrogels demonstrated a lower swelling capacity, higher rheological properties and compressive modulus, and slow degradation behavior at higher content, likely due to the higher degree of cross-linking. An experiment with cells indicated the good cell compatibility of these hydrogels, as revealed by Cell Counting Kit-8 (CCK-8) assays. As a tissue-engineered material, this photo-cross-linkable SFMA is expected to have a wide range of applications in the biomedical field.

9.
Comput Assist Surg (Abingdon) ; 27(1): 63-73, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35882055

RESUMO

BACKGROUND: Though some studies have reported navigated high tibial osteotomy (HTO) is a useful procedure to correct knee deformity. There is still great controversy whether navigated HTO can achieve better accuracy of limb alignment and greater clinical outcomes. Current meta-analysis was conducted to investigate whether better radiographic outcomes and clinical outcomes could be acquired in navigated HTO compared with the conventional procedure. METHOD: We conducted a literature search in the electronic databases, including Medline, Embase, the Cochrane Library, and Web of Science. We identified studies published before August 2020. We also checked the references of the related articles for any relevant studies. We strictly followed the Preferred Reporting Items for Systematics reviews and Meta-Analysis (PRISMA) guidelines in this review. This research was performed using Review Manager 5.4 software. RESULTS: Fourteen articles were included, involving 1399 knees. Our meta-analysis indicated that patients undergoing navigated HTO had significantly better outcomes in outliers of aimed limb alignment (RD=-0.24, 95% CI: =-0.34 to -0.13, p < 0.01), outliers of aimed tibial posterior slope (TPS) (RD=-0.41, 95% CI: -0.51 to -0.30, p < 0.01), Range of Motion (ROM) (MD = 6.37, 95%CI: 0.83-11.91, p = 0.02), and American knee society knee score (AKS knee score) (MD = 3.88, 95%CI: 1.37-6.39, p = 0.002). No significant differences were found in Lysholm score (MD = 1.30, 95%CI: -0.31 to 2.90, p = 0.11), American knee society function score (AKS function score) (RD = 1.42, 95%CI: -0.15 to 2.99, p = 0.08), complications (RD=-0.01, 95% CI: = -0.05 to 0.04, p = 0.77), delayed union (RD=-0.01, 95% CI: = -0.02 to 0.03, p = 0.59), and reoperation (RD = 0, 95% CI: -0.09 to 0.10, p = 0.98) between the two groups. The operation time in the navigated group was 15.46 min longer than in the conventional group. CONCLUSION: Navigated HTO provided more accurate and reproducible radiographic outcomes in the correction of the malalignment than conventional techniques, and there is no difference in the risk of complications compared with conventional HTO. However, it is unclear whether navigation HTO can achieve better clinical results. More randomized controlled trials (RCTs) with high quality, large sample size, and sufficient follow-up period are required.


Assuntos
Osteoartrite do Joelho , Computadores , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Tecnologia
10.
J Pharm Sci ; 110(1): 268-279, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32663595

RESUMO

The aim of the study is to design octaarginine (R8)-modified insulin-alginate nanoparticles (INS-SA/R8 NPs) as the oral insulin delivery system, and further investigate its penetrating mechanism. The characterization results indicated that the surface of INS-SA/R8 NPs was smooth and the average diameter was about 300 nm. INS-SA/R8 NPs exhibited a stronger stability in the simulated gastrointestinal fluids and had a better controlled release than unmodified alginate nanoparticles (INS-SA NPs). Moreover, INS-SA/R8 NPs group had the strongest insulin transport capacity and the largest amount of insulin uptake in all experimental groups. Most importantly, the improvement of insulin intestinal uptake was further confirmed in rat intestine in vivo, and its penetrating mechanism might be involved in the production of endogenous nitric oxide (NO) signal molecule. In addition, in vivo hypoglycemic studies showed that orally administrated INS-SA/R8 NPs produced a better hypoglycemic effect as compared with INS-SA NPs in diabetic rats. Meanwhile, from the cytotoxicity analysis, INS-SA/R8 NPs were safe for oral administration. Taken together, INS-SA/R8 NPs was a good oral insulin delivery system, which might also be suitable for other protein drugs.


Assuntos
Diabetes Mellitus Experimental , Nanopartículas , Administração Oral , Alginatos , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Intestinos , Oligopeptídeos , Ratos
11.
Acta Psychol (Amst) ; 208: 103101, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32485339

RESUMO

The low spatial frequency (LSF) component of visual information rapidly conveyed coarse information for global perception, while the high spatial frequency (HSF) component delivered fine-grained information for detailed analyses. The feedforward theorists deemed that a coarse-to-fine process was sufficient for a rapid scene recognition. Based on the response priming paradigm, the present study aimed to deeply explore how different spatial frequency interacted with each other during rapid scene recognition. The response priming paradigm posited that as long as the prime slide could be rapidly recognized, the prime-target system was behaviorally equivalent to a feedforward system. Adopting broad spatial frequency images, experiment 1 revealed a typical response priming effect. But in experiment 2, when the HSF and the LSF components of the same pictures were separately presented, neither the LSF-to-HSF sequence nor the HSF-to-LSF sequence reproduced the response priming effect. These results demonstrated that LSF or HSF component alone was not sufficient for rapid scene recognition and, further, that the integration of different spatial frequency needed some early feedback loops. These findings supported that the local recurrent processing loops among early visual cortex was involved during rapid scene recognition.


Assuntos
Reconhecimento Psicológico , Córtex Visual , Percepção Visual , Humanos , Reconhecimento Visual de Modelos , Estimulação Luminosa
12.
Materials (Basel) ; 12(7)2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30935052

RESUMO

Lithium-ion batteries are widely used as basic power supplies and storage units for large-scale electric drive products such as electric vehicles. Their reliability is directly related to the life and safe operation of the electric drive products. In fact, the cells have a dependent relationship with the degradation process and they affect the degradation rate of the entire battery pack, thereby affecting its reliability. At present, most research focuses on the reliability of battery packs and assumes that their cells are independent of each other, which may cause the reliability of the evaluation to deviate greatly from the actual level. In order to accurately assess the reliability of lithium-ion batteries, it is necessary to build a reliability model considering the dependency among cells for the overall degradation of lithium-ion battery packs. Therefore, in this study, based on a lithium-ion battery degradation test, the Wiener process is used to analyze the reliability of four basic configurations of lithium-ion battery packs. According to the degradation data of the battery packs, the Copula function is used to quantitatively describe the dependent relationship in the degradation process of a single battery, and the quantitative dependent relationship is combined with the reliability model to form a new reliability model. Finally, taking the battery system of Tesla S as an example, a feasible optimization method for battery pack design is provided based on the model constructed in this work.

13.
Int J Biol Macromol ; 122: 1120-1127, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30218732

RESUMO

In this study, the collagen/chitosan gel composite supplemented with a cell-penetrating peptide (CPP) (Oligoarginine, R8) was prepared. Then, the physicochemical properties of the new collagen/chitosan/CPPs gel obtained were analyzed and the related characteristics were evaluated by scanning electron microscopy (SEM), fourier transform infrared (FTIR), differential scanning calorimetry (DSC), differential thermal analyzer (DTA). Furthermore, we found that collagen/chitosan/CPPs gel composite was capable of inhibiting Staphylococcus aureus growth and had good ability to heal wounds. The mice test results showed that collagen/chitosan/CPPs gel had the highest healing rate, fastest healing speed in all the treatments. After 14 days, the group treated by collagen/chitosan/CPPs gel showed nearly complete wound surface healing rate of 98 ±â€¯4.71%. In addition, histopathological examination suggested that collagen/chitosan/CPPs could promote cutaneous wound healing through enhancing granulation tissue formation, increasing collagen deposition and promoting angiogenesis in the wound tissue. Meanwhile, no significant cytotoxicity of the gel was observed. In conclusion, the collagen/chitosan/CPPs gel composite which has antibacterial activity renders a high therapeutic efficiency to heal wounds.


Assuntos
Quitosana/química , Colágeno/química , Peptídeos/química , Peptídeos/farmacologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Hidrogéis/química , Camundongos , Staphylococcus aureus/efeitos dos fármacos
14.
Audiol Neurootol ; 13(5): 302-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18391566

RESUMO

The aim of this study was to assess the verbal and performance intelligence of young Mandarin-speaking cochlear implant users with the Wechsler Intelligence Scale for Children (WISC). We also analyzed whether related factors helped develop verbal and performance IQs. We studied 60 children implanted with Nucleus 24 devices; the children represented a consecutive sample of every implantee aged 6 or older from 2002 to 2006. All subjects had 1 year to 8 years and 7 months of implant experience. Five children with known neurological, developmental delay and multiple handicaps were excluded. Intellectual functions were evaluated using the Mandarin version of the WISC-III, which includes 5 subsets for verbal IQ (information, comprehension, similarities, arithmetic and vocabulary) and 5 subsets for performance IQ (picture completion, picture arrangement, block design, object assembly and coding). After conversion, we found that the mean verbal IQ was 85.1 +/- 19.9 (range 56-133), and the mean performance IQ was 99.2 +/- 15.9 (range 61-131). The distribution of verbal IQ was significantly different from that of the hearing population. A much larger proportion (32%) falls into the category of 'intellectual deficiency' and a relatively smaller proportion in the 'average' and 'above average' level. As for performance IQ, the distribution was not significantly different from the norms. Regarding the possibly related factors, univariate and multivariate linear regression showed that the verbal IQ was significantly affected by gender (female > male, p = 0.004), side of implantation (bilateral > left > right, p = 0.017) and two speech test scores (PB score, p = 0.036; sentence, p = 0.002), but not by age at implantation (p = 0.621) or length of implant usage (p = 0.480). Only a moderate correlation (r = 0. 49) was found between verbal and performance IQ. In conclusion, we have demonstrated that the performance IQ for the cochlear implant users is not different from their counterparts with normal hearing. However, the distribution of verbal IQ significantly shifts to the left. Our findings suggest that the verbal IQ test may just be another measurement of spoken language outcomes or learning skills and therefore may not represent the 'true intelligence' of these cochlear implant users.


Assuntos
Desenvolvimento Infantil , Implantes Cocleares , Perda Auditiva Neurossensorial/psicologia , Perda Auditiva Neurossensorial/cirurgia , Inteligência , Escalas de Wechsler/normas , Adolescente , Povo Asiático , Criança , Feminino , Humanos , Modelos Lineares , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Percepção da Fala
15.
Int J Biol Macromol ; 111: 685-695, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29343452

RESUMO

In this study, a cell-penetrating peptide conjugate, R8-carboxymethyl-ß-cyclodextrin (R8-CM-ß-CD), was synthesized, and then we prepared the supramolecular complex (insulin/R8-CM-ß-CD). The physicochemical properties of the complex were characterized. The supramolecular complex could facilitate the uptake of insulin, meanwhile, induce a significantly higher internalization of insulin. Interestingly, the transportation efficiency of insulin/R8-CM-ß-CD across the Caco-2 cell monolayer was about 3 times greater than that of insulin/CM-ß-CD. Further studies on the mechanism in increasing uptake efficiency showed that R8-CM-ß-CD was internalized via different styles of endocytosis and could inhibit P-glycoprotein (P-gp) efflux pumps. Importantly, the formulation of insulin/R8-CM-ß-CD showed the highest increase in the permeability of insulin and the best biological response in diabetic rats of all the treatments. In addition, no sign of toxicity was observed after administrations of R8-CM-ß-CD. These results demonstrated that R8-CM-ß-CD was a promising carrier for use in protein drug delivery.


Assuntos
Peptídeos Penetradores de Células/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Insulina/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Peptídeos Penetradores de Células/química , Diabetes Mellitus Experimental/patologia , Endocitose/efeitos dos fármacos , Humanos , Hipoglicemiantes , Insulina/química , Absorção Intestinal/efeitos dos fármacos , Nanopartículas/administração & dosagem , Nanopartículas/química , Ratos , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/química
16.
Oncol Rep ; 36(4): 2079-86, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27572553

RESUMO

Previous studies reported that the aberrant expression of miR-19b in gastric cancer tissues and circulating miR-19b is a potential biomarker to indicate progression of gastric cancer. However, the prognostic significance of miR-19b, and its role and underlying mechanisms in gastric cancer remain poorly investigated. In the present study, we demonstrated that the expression of miR-19b was aberrantly downregulated in both gastric cancer tissues and cell lines. Clinical association analyses disclosed that the reduced expression of miR-19b was significantly associated with adverse clinicopathological characteristics including poor differentiation, large tumor size and advanced tumor-node-metastasis (TNM) stage. Gastric cancer patients with low expression of miR-19b had prominent shorter overall survival and disease-free survival. Gain-of-function studies indicated that miR-19b overexpression inhibited cell proliferation and cell cycle progression in MGC-803 cells. While miR-19b silencing promoted cell proliferation and cell cycle progression in SGC-7901 cells. Furthermore, in vivo experiments showed that miR-19b overexpression suppressed the tumor growth of MGC-803 cells. Notably, miR-19b inversely regulated B-cell CLL/lymphoma 3 (BCL3) abundance in gastric cancer cells. BCL3 was identified as a direct target of miR-19b using luciferase reporter assays. Moreover, BCL3 knockdown abolished the effects of miR-19b knockdown on gastric cancer cells. In conclusion, our data suggest that miR-19b may potentially serve as a novel prognostic biomarker and therapeutic target for gastric cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas/biossíntese , Neoplasias Gástricas/patologia , Fatores de Transcrição/biossíntese , Adulto , Idoso , Animais , Proteína 3 do Linfoma de Células B , Western Blotting , Proliferação de Células/genética , Intervalo Livre de Doença , Regulação para Baixo , Feminino , Xenoenxertos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Fatores de Transcrição/genética , Transfecção
17.
J Dermatol Sci ; 82(1): 28-37, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26829882

RESUMO

BACKGROUND: Skin wound healing is a complex process that repairs multiple organ-tissues. Fibroblasts are key players of skin cells, whose migration is important during wound healing process. bFGF has shown a great efficacy to promote cell migration, but the precise mechanism by which bFGF regulates cell migration remains elusive. OBJECTIVE: The aim of this study was to find bFGF-regulated gene pools and further identify target molecules that participated in human fibroblast cell migration. METHODS: Skin primary fibroblasts and rat skin wound model were used to demonstrate the novel mechanism of bFGF regulating cell migration to accelerate wound healing. Cell migration was determined using the wound healing scratch assay. The differentially expressed genes and numerous biochemical pathways after bFGF treatment were identified by RNA-Seq analysis, and differentially expressed genes were further verified by qRT-PCR. siRNA duplex target to interfering the expression of PI3-kinase (p110α) was transformed into NIH/3T3 cells. Western blotting analysis was used to determine marker protein expressions. The invasive activity of fibroblasts was measured using 3D spheroid cell invasion assay. RESULTS: RNA-Seq analysis identified numerous biochemical pathways including the NF-κB pathway under the control of FGF signaling. bFGF negatively regulates the phosphorylation of IκB-α, the most well studied NF-κB signaling regulator while bFGF induces JNK phosphorylation. Application of Bay11-7082, a representative NF-κB inhibitor promoted cell migration, invasion and enhanced the JNKs phosphorylation. However, inhibition of JNKs blocked cell migration when NF-κB is inhibited. Moreover, application of the PI3K inhibitor LY294002 together with Bay11-7082 maintained normal cell migration and knocking-down PI3K (p110α) by a specific siRNA inhibited JNKs phosphorylation while maintaining normal IκBα phosphorylation, indicating that PI3K and NF-κB signaling independently regulate JNKs activation. In addition, administration of bFGF or Bay11-7082 promoted rat skin wound repair and accelerated the invasion of fibroblasts. CONCLUSION: This study sheds light on the mode of action of bFGF and identifies that the NF-κB-JNKs pathway is independent of the PI3K-JNKs pathway to accelerate fibroblast migration. In addition, bFGF and the relief of inflammation could be a favorable therapeutic approach for skin wound healing.


Assuntos
Movimento Celular/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Fibroblastos/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Classe I de Fosfatidilinositol 3-Quinases , Ativação Enzimática , Fibroblastos/enzimologia , Perfilação da Expressão Gênica , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Masculino , Camundongos , Modelos Animais , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Células NIH 3T3 , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Ratos Sprague-Dawley , Fatores de Tempo , Transfecção , Proteínas rac1 de Ligação ao GTP/genética
18.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 29(6): 422-7, 2013 Nov.
Artigo em Zh | MEDLINE | ID: mdl-24624879

RESUMO

OBJECTIVE: To explore the clinical classification method of keloids and providing a thread for the treatment of keloids. METHODS: To summarize the 600 cases of keloid patients we accepted and diagnosed from November 2004 to October 2012, and filling in keloid patients information sheet, recording the keloids form by photographs, analyzing the treatment, putting forward the classification method of keloids in clinic. RESULTS: According to the position and quantity that keloids grow, the keloid patients are divided into four major categories:one in single site, one in each site, more than one in single site and more than one in each site; According to the area and thickness of keloids, the keloid single lesion is divided into four subclasses: type of small area and thin, type of small area and thick, type of large areas and thin,type of large areas and thick; According to the number of lesions, keloid multiple lesions is divided into two subgenera: isolated multiple and dispersion multiple, different kinds of keloids suit different methods of treatment. CONCLUSION: The clinical classification method of keloids can be used to provide thought for the treatment of keloids, and have a good application value.


Assuntos
Queloide/classificação , Queloide/patologia , Humanos , Queloide/terapia
20.
Artigo em Inglês | MEDLINE | ID: mdl-15583439

RESUMO

The purpose of this study is to compare speech perception performance in Mandarin-speaking Nucleus CI24 implantee using standard behavior MAPs and NRT-based MAPs. Eight Nucleus CI24 users (5 years and older) participated in the study. They all fulfilled the following criteria: (1) behavioral MAP and NRT thresholds can be reliably obtained; (2) had more than 18 functioning electrodes; (3) had at least 6 months experience using CI. All subjects received speech evaluation under three different MAPs: a traditional behavioral MAP, a MAP predicted from the NRT thresholds of the E22 (electrode 22), E19, E15, E11, E8, E5, E1 and a combined MAP based on the information of NRT thresholds and behavioral threshold/comfortable levels of the E11. The speech evaluation package included word recognition test in quiet, in noise, and a Mandarin sentence test in quiet. Results showed that three MAPs are similar in some subjects, but different in other subjects. Compared to the NRT MAPs, the combined MAPs are more similar to the behavioral MAPs. There was no significant difference in the mean score of the word recognition test in quiet, in noise and sentence test under these three MAP conditions. In conclusion, although the behavioral MAPs and the NRT-based MAPs are not identical, the speech performance of Mandarin-speaking CI24 implantee using MAPs predicted from NRT thresholds appeared to be no worse than the traditional behavioral MAPs. Therefore, in certain cases that behavioral MAPs are difficult to obtain (such as in very young or multiple handicapped children), NRT-based MAPs may serve reliably as an initial estimation.


Assuntos
Potenciais de Ação/fisiologia , Limiar Auditivo/fisiologia , Comportamento/fisiologia , Implantes Cocleares , Nervo Coclear/fisiopatologia , Percepção da Fala , Adolescente , Adulto , Criança , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Telemetria
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