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1.
Drugs Context ; 122023.
Artigo em Inglês | MEDLINE | ID: mdl-37415916

RESUMO

Preventing abnormal scar formation and correcting non-aesthetic mature scars are important to prevent physical and psychosocial consequences of abnormal scarring. Evidence-based guidelines for scar management in Asian patients recommend first-line silicone-based products. Dermatix®* Ultra and Dermatix Ultra Kids are topical silicone gels containing a vitamin C ester that helps lighten scar tissue. Herein, we report a case series including patients with hypertrophic and keloid scars treated with Dermatix, showing that Dermatix is effective for scar treatment and prevention, as well as expert consensus supporting the safe and effective use of Dermatix.

2.
Comput Biol Chem ; 93: 107515, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34044204

RESUMO

Because of rapid advancements in sequencing technology, the experimental platforms of RNA-seq are updated frequently. It is quite common to combine data sets from several experimental platforms for analysis in order to increase the sample size and achieve more powerful tests for detecting the presence of differential gene expression. The data sets combined from different experimental platforms will have a complex data distribution, which causes a major problem in statistical modeling as well as in multiple testing. Although plenty of research have studied this problem by modeling the batch effects, there are no general and robust data-driven procedures for RNA-seq analysis. In this paper we propose a new robust procedure which combines the use of popular methods (packages) with a data-driven simulation (DDS). We construct the average receiver operating characteristic curve through the DDS to provide the calibrated levels of significance for multiple testing. Instead of further modifying the adjusted p-values, we calibrated the levels of significance for each specific method and mean effect model. The procedure was demonstrated with several popular RNA-seq analysis methods (edgeR, DEseq2, limma+voom). The proposed procedure relaxes the stringent assumptions of data distributions for RNA-seq analysis methods and is illustrated using colorectal cancer studies from The Cancer Genome Atlas database.


Assuntos
Adenocarcinoma/genética , Neoplasias do Colo/genética , Simulação por Computador , Análise de Sequência de RNA , Calibragem , Humanos
3.
Healthcare (Basel) ; 9(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466527

RESUMO

Hemodialysis (HD) patients are highly susceptible to COVID-19 infection. However, comprehensive assessments of current evidence regarding COVID-19 in HD patients remain incomplete. We systematically searched PUBMED and EMBASE for articles published on incidence or mortality of COVID-19 infection in HD patients until September 2020. Two independent researchers extracted data and study-level risk of bias across studies. We conducted meta-analysis of proportions for incidence and mortality rate. Study heterogeneity and publication bias were assessed. A total of 29 articles with 3261 confirmed COVID-19 cases from a pool of 396,062 HD patients were identified. Incidence of COVID-19 in these HD patients was 7.7% (95% CI: 5.0-10.9%; study heterogeneity: I2 = 99.7%, p < 0.001; risk of publication bias, Egger's test, p < 0.001). Overall mortality rate was 22.4% (95% CI: 17.9-27.1%; study heterogeneity: I2 = 87.1%, p < 0.001; risk of publication bias, Egger's test: p = 0.197) in HD patients with COVID-19. Reported estimates were higher in non-Asian than Asian countries. Quality of study may affect the reported incidence but not the mortality among studies. Both incidence and mortality of COVID-19 infection were higher in HD patients. Available data may underestimate the real incidence of infection. International collaboration and standardized reporting of epidemiological data should be needed for further studies.

4.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20061291

RESUMO

The COVID-19 pandemic has caused a worldwide shortage of personal protective equipment including N95 and FFP3 respirators. Reusable elastomeric respirators are suitable alternatives when used with compatible filters. These filters may be difficult to source and elastomeric respirators are not recommended for surgical use as the exhaled air is not filtered. Breathing system filters are routinely used in anaesthetic circuits to filter virus and bacteria. In this study, we designed 3D printed adapters that allowed elastomeric respirators to utilise breathing system filters and made simple modifications to the respirators to filter exhaled breaths. We then evaluated the performance and safety of our modified elastomeric respirators with quantitative fit tests. We recruited 8 volunteers to perform quantitative fit tests. Fit factors, respiratory rate and end-tidal carbon dioxide were recorded before and after wearing the modified respirators for 1 hour. All 8 volunteers obtained fit factors of 200+, the maximum achievable, for all tests exercises in all fit tests. The mean (range) end-tidal carbon dioxide was 4.5 (3.9-5.5) kPa and 4.6 (range 4.1-5.3) kPa before and after 1 hour of usage. The mean (range) respiratory rate was 16.5 (11-24) min-1 and 17.4 (15-22) min-1 before and after 1 hour of usage. Four (50%) did not experience any subjective discomfort while 2 (25%) reported pressure on the face, 1 (12.5%) reported exhalation resistance and 1 (12.5%) reported transient dizziness with exertion. Breathing system filters combined with properly fitted reusable elastomeric respirators is a safe alternative to N95 during the COVID-19 pandemic.

5.
BMC Cancer ; 19(1): 1167, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791269

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy. METHODS: Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45- cells and cCSCs as CD133+EpCAM+Hoechst+CD45- cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses. RESULTS: We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS. CONCLUSIONS: Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Células Neoplásicas Circulantes/patologia , Células-Tronco Neoplásicas/patologia , Antígeno AC133/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Contagem de Células , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/imunologia , Células-Tronco Neoplásicas/imunologia , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
6.
Int J Oncol ; 55(4): 938-948, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485600

RESUMO

Liposarcoma (LPS) is one of the most frequently reported type of soft­tissue sarcoma (STS). Well­differentiated (WD) LPS and dedifferentiated (DD) LPS are the two most common subtypes. Chemotherapy has been considered to be ineffective in LPS, and novel treatment agents are thus necessary. In this study, we reanalyzed two published microarray data sets of LPS. By comparing the top 50 upregulated genes in DD LPS in both sets of data, we identified 12 overlapping genes. Of note, the top five gene sets enriched in DD LPS in both sets of data were involved in cell cycle regulation. Among the 12 overlapping genes, aurora kinase A (AURKA) is a well­known gene involved in cell cycle regulation; we thus further investigated this gene. AURKA was significantly upregulated in DD LPS, compared with WD LPS. Among 40 cases of DD LPS in GSE30929, patients with high AURKA expression in tumors had significantly worse distant recurrence­free survival than those with low expression. In an in vitro model, MLN8237, an AURKA inhibitor, could inhibit AURKA in LPS cell lines with a resultant G2/M arrest. MLN8237 was also reported to exert a cytotoxic effect by inducing apoptosis in LPS cell lines. Furthermore, except for cisplatin, MLN8237 had a significantly synergistic effect with chemotherapy agents against LPS. MLN8237 induced cellular senescence in LPS cell lines with increased expression of DcR2, a senescence biomarker, and upregulated expression of cytokines associated with the senescence­associated secretory phenotype, including interleukin (IL)­1α, IL­6 and IL­8. Our study identified AURKA as a potential biomarker for predicting poor prognosis in LPS. The findings of the present study suggested the potential of AURKA as a therapeutic target in LPS cell line models, while the novel combination of AURKA inhibitors and chemotherapy requires further investigation.


Assuntos
Aurora Quinase A/genética , Azepinas/farmacologia , Perfilação da Expressão Gênica/métodos , Lipossarcoma/genética , Pirimidinas/farmacologia , Aurora Quinase A/antagonistas & inibidores , Desdiferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Tratamento Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lipossarcoma/tratamento farmacológico , Análise de Sequência com Séries de Oligonucleotídeos , Regulação para Cima/efeitos dos fármacos
7.
Int J Oncol ; 55(2): 536-546, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31268158

RESUMO

Gastrointestinal stromal tumors (GISTs) are gastrointestinal tract sarcomas that commonly contain a mutation in the tyrosine kinases, KIT and platelet­derived growth factor receptor A (PDGFRA). Imatinib, sunitinib and regorafenib are all effective tyrosine kinase inhibitors; however, acquired resistance is inevitable. The E26 variant 1 (ETV1) pathway has been found to be a key downstream effector of KIT and is therefore a reasonable therapeutic target for this disease. In this study, we explored the potential agents targeting ETV1 in GISTs by uploading an ETV1 knockout gene signature of GIST cell lines to the pattern­matching software 'Connectivity Map'. The activity and mechanisms of identified agents were examined using an in vitro model. Four drugs were identified: Suberanilohydroxamic acid and trichostatin [two histone deacetylase inhibitors (HDACIs)] and trifluoperazine and thioridazine (two phenothiazine­class drugs). Western blot analysis demonstrated that all four drugs had ETV1­downregulating effects. As HDACIs have been previously studied in GISTs, we focused on phenothiazine. Phenothiazine was found to exert cytotoxicity and to induce apoptosis and autophagy in GISTs. Treatment with phenothiazine had little effect on the KIT/AKT/mammalian target of rapamycin (mTOR) pathway, but instead upregulated extracellular­signal­regulated kinase (ERK) activity. A combination of phenothiazine and a MEK inhibitor had a synergistic cytotoxic effect on GISTs. Western blot analysis indicated that ELK1 and early growth response 1 (EGR1) were activated/upregulated following phenothiazine treatment, and the MEK inhibitor/phenothiazine combination downregulated the ERK/ELK1/EGR1 pathway, resulting in diminished autophagy, as well as enhanced apoptosis. On the whole, the findings of this study established phenothiazine as a novel class of therapeutic agents in GIST treatment and demonstrate that a combination of phenothiazine and MEK inhibitor has great potential for use in the treatment of GISTs.


Assuntos
Biomarcadores Tumorais/genética , Conectoma , Proteínas de Ligação a DNA/antagonistas & inibidores , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fenotiazinas/farmacologia , Fatores de Transcrição/antagonistas & inibidores , Antineoplásicos/farmacologia , Antiprotozoários/farmacologia , Apoptose , Proteínas de Ligação a DNA/genética , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Perfilação da Expressão Gênica , Humanos , Prognóstico , Transdução de Sinais , Fatores de Transcrição/genética
8.
J Craniomaxillofac Surg ; 47(8): 1185-1189, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31182256

RESUMO

OBJECTIVES/HYPOTHESIS: The objective of this study was to systematically review the English literature for articles that have described skeletal surgeries in the treatment of obstructive sleep apnea in both adults and children. From these articles trends and patterns in the treatment of OSA with skeletal procedures are described. STUDY DESIGN: Three databases including MEDLINE, Google Scholar and the Cochrane Library were searched through May 1, 2018. METHODS: The systematic and independent literature reviews were performed and the determination of included studies was made by consensus. Relevant studies were examined based on six categories of skeletal surgery: 1) Hyoid Advancement 2) Genioplasty/Genioglossus Advancement 3) Maxillary Expansion 4) Maxillomandibular Advancement 5) Mandibular Distraction and 6) Maxillomandibular Expansion. RESULTS: 1875 studies were analyzed for inclusion of which 414 were ultimately included in our analysis. A steady increase in the publication of articles pertaining to maxillary expansion and maxillomandibular advancement was identified. Research interest in hyoid advancement and genioplasty/genioglossus advancement has declined in the past decade. CONCLUSIONS: Changing trends in skeletal surgery for OSA offer exciting and efficacious therapeutic surgical modalities. MMA is the most widely studied and efficacious multi-level surgery for OSA today. Newer modalities such as adult maxillary expansion offer encouraging early results with minimal complication rates, and further study should be directed in this area.


Assuntos
Avanço Mandibular , Apneia Obstrutiva do Sono , Mentoplastia , Humanos , Osso Hioide , Maxila , Apneia Obstrutiva do Sono/cirurgia , Resultado do Tratamento
9.
Schizophr Res ; 188: 63-67, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28108227

RESUMO

Patients with schizophrenia have a higher risk of cardiovascular diseases and higher mortality from them than does the general population; however, the underlying mechanism remains unclear. Impaired cerebral autoregulation is associated with cerebrovascular diseases and their mortality. Increased or decreased cerebral blood flow in different brain regions has been reported in patients with schizophrenia, which implies impaired cerebral autoregulation. This study investigated the cerebral autoregulation in 21 patients with schizophrenia and 23 age- and sex-matched healthy controls. None of the participants had a history of cardiovascular diseases, hypertension, or diabetes. All participants underwent 10-min blood pressure and cerebral blood flow recording through finger plethysmography and Doppler ultrasonography, respectively. Cerebral autoregulation was assessed by analyzing two autoregulation indices: the mean blood pressure and cerebral blood flow correlation coefficient (Mx), and the phase shift between the waveforms of blood pressure and cerebral blood flow determined using transfer function analysis. Compared with the controls, the patients had a significantly higher Mx (0.257 vs. 0.399, p=0.036) and lower phase shift (44.3° vs. 38.7° in the 0.07-0.20Hz frequency band, p=0.019), which indicated impaired maintenance of constant cerebral blood flow and a delayed cerebrovascular autoregulatory response. Impaired cerebral autoregulation may be caused by schizophrenia and may not be an artifact of coexisting medical conditions. The mechanism underlying impaired cerebral autoregulation in schizophrenia and its probable role in the development of cerebrovascular diseases require further investigation.


Assuntos
Circulação Cerebrovascular , Transtornos Cerebrovasculares/fisiopatologia , Homeostase , Esquizofrenia/fisiopatologia , Adulto , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Circulação Cerebrovascular/fisiologia , Transtornos Cerebrovasculares/diagnóstico por imagem , Feminino , Dedos/irrigação sanguínea , Dedos/fisiopatologia , Homeostase/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pletismografia , Esquizofrenia/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana
10.
BMC Urol ; 16(1): 67, 2016 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-27852299

RESUMO

BACKGROUND: Anxiety disorders (ADs) are common with a high rate of medical comorbidities. Although the association between ADs and the overall cancer risk remains controversial, patients with ADs were found to be more likely to develop specific cancer types. Herein, we estimated the risk of developing urological cancers among patients with ADs in a 5-year follow-up period using a population-based database. METHODS: Two study cohorts were identified from the Taiwan Longitudinal Health Insurance Database 2005: patients with ADs, and comparison subjects selected by one-to-one matching for sex, age, and the year of recruitment. Follow-up was undertaken to determine whether sampled patients and comparison subjects had developed urological cancers in the subsequent 5 years. RESULTS: We found that urological cancers occurred among 0.54% of patients with ADs and 0.13% of comparison subjects. After adjusting for sociodemographic characteristics, medical comorbidities, and alcohol and tobacco use disorder, the stratified Cox proportional hazard regression suggested that patients with ADs were more likely to develop urological cancers relative to comparison subjects (adjusted hazard ratio, 3.67; 95% confidence interval, 2.85 ~ 4.72). The adjusted HR for males with ADs was 3.82 (95% CI: 2.79 ~ 5.23) in comparison to males without ADs. In addition, the adjusted HR for females with ADs was 3.47 (95% CI: 2.26 ~ 5.31) than those females without ADs. CONCLUSIONS: We concluded that during the 5-year follow-up period, there was a significantly increased risk of urological cancers among patients with ADs.


Assuntos
Transtornos de Ansiedade/complicações , Neoplasias Urológicas/epidemiologia , Neoplasias Urológicas/etiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco
11.
Int J Oncol ; 48(3): 1187-94, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26794530

RESUMO

Polo-like kinase 1 (PLK1), a serine/threonine kinase and an oncogene, is crucial in regulating cell cycle progression. PLK1 also has been demonstrated as a potential target of osteosarcoma (OS) by using short hairpin RNA libraries in lentiviral vectors for screening of protein kinase. In preclinical studies, GSK461364, a potent and selective ATP-competitive PLK1 inhibitor, showed antiproliferative activity against multiple tumor cell lines. In the present study, we evaluated the expression level of PLK1 in OS and explored the cytotoxic mechanism of GSK461364 against OS. PLK1 was significantly overexpressed in OS compared with normal osteoblasts and other types of sarcoma. GSK461364 inhibited PLK1 and caused mitotic arrest by inducing G2/M arrest in OS cells. Moreover, GSK461364 exerted a cytotoxic effect by inducing apoptosis in OS, and induced cellular senescence in OS cell lines, as indicated by an increased senescence-associated ß-galactosidase activity and enhanced DcR2 and interleukin-1α expression. In addition, we demonstrated a synergistic cytotoxic effect of GSK461364 and paclitaxel, possibly resulting from combined mitotic arrest. In conclusion, the present study revealed that PLK1 was overexpressed in OS and that GSK461364 exerted its cytotoxic effect on OS by inducing mitotic arrest and subsequent apoptosis and induced cellular senescence; therefore, senescence-associated markers can be used as treatment biomarkers, and a combination of GSK461364 and paclitaxel can potentially treat OS.


Assuntos
Benzimidazóis/química , Proteínas de Ciclo Celular/antagonistas & inibidores , Inibidores Enzimáticos/química , Osteossarcoma/metabolismo , Paclitaxel/química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Tiofenos/química , Trifosfato de Adenosina/química , Apoptose , Ciclo Celular , Diferenciação Celular , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células , Sobrevivência Celular , Senescência Celular , Biologia Computacional , Sinergismo Farmacológico , Citometria de Fluxo , Humanos , Mitose , Análise de Sequência com Séries de Oligonucleotídeos , Osteoblastos/metabolismo , RNA Interferente Pequeno/metabolismo , beta-Galactosidase/metabolismo , Quinase 1 Polo-Like
12.
Oncotarget ; 5(12): 4071-86, 2014 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-24901229

RESUMO

Although imatinib mesylate (IM) has revolutionized the management of gastrointestinal stromal tumors (GISTs), drug resistance remains a challenge. Previous studies have shown that the expression of aurora kinase A (AURKA) predicts recurrence in patients with primary, surgically resected GISTs. The current study aimed to evaluate the significance of AURKA expression as an unfavorable prognostic marker for advanced GISTs, and provide evidence that AURKA could be a potential therapeutic target in GISTs. The prognostic significance of the expression of AURKA, along with other clinicopathological factors, was analyzed in a cohort of 99 IM-treated patients with advanced GISTs. The potential use of an inhibitor of AURKA as a therapeutic agent against GISTs was also tested in GIST cell lines. Among 99 enrolled patients, poor performance status, large tumor size, drug response, and AURKA overexpression were independent prognostic factors for poor progression-free survival (PFS). For overall survival (OS), only large tumor size and AURKA overexpression were identified as independent unfavorable factors. In an in vitro study, MLN8237, an AURKA inhibitor, inhibited growth of both IM-sensitive and IM-resistant GIST cells in a concentration-dependent manner, and exhibited synergistic cytotoxicity with IM in GIST cells. The inhibitory effect of MLN8237 in GIST cells could be attributed to the induction of G2/M arrest, apoptosis, and senescence. Our study shows that AURKA expression independently predicted poor PFS and OS in patients with advanced GISTs who were treated with IM. An AURKA inhibitor may have potential as a therapeutic agent for both IM-sensitive and IM-resistant GISTs.


Assuntos
Aurora Quinase A/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Senescência Celular , Intervalo Livre de Doença , Humanos , Metástase Neoplásica , Prognóstico , Resultado do Tratamento
13.
Oncotarget ; 5(3): 716-25, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24566468

RESUMO

Polo-like kinase 1 (PLK1), a critical cell cycle regulator, has been identified as a potential target in osteosarcoma (OS). 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2), a prostaglandin derivative, has shown its anti-tumor activity by inducing apoptosis through reactive oxygen species (ROS)-mediated inactivation of v-akt, a murine thymoma viral oncogene homolog, (AKT) in cancer cells. In the study analyzing its effects on arthritis, 15d-PGJ2 mediated shear-induced chondrocyte apoptosis via protein kinase A (PKA)-dependent regulation of PLK1. In this study, the cytotoxic effect and mechanism underlying 15d-PGJ2 effects against OS were explored using OS cell lines. 15d-PGJ2 induced significant G2/M arrest, and exerted time- and dose-dependent cytotoxic effects against all OS cell lines. Western blot analysis showed that both AKT and PKA-PLK1 were down-regulated in OS cell lines after treatment with 15d-PGJ2. In addition, transfection of constitutively active AKT or PLK1 partially rescued cells from 15d-PGJ2-induced apoptosis, suggesting crucial roles for both pathways in the anti-cancer effects of 15d-PGJ2. Moreover, ROS generation was found treatment with 15d-PGJ2, and its cytotoxic effect could be reversed with N-acetyl-l-cysteine. Furthermore, inhibition of JNK partially rescued 15d-PGJ2 cytotoxicity. Thus, ROS-mediated JNK activation may contribute to apoptosis through down-regulation of the p-Akt and PKA-PLK1 pathways. 15d-PGJ2 is a potential therapeutic agent for OS, exerting cytotoxicity mediated through both AKT and PKA-PLK1 inhibition, and these results form the basis for further analysis of its role in animal studies and clinical applications.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Prostaglandina D2/análogos & derivados , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Osteossarcoma/patologia , Fosforilação , Prostaglandina D2/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Quinase 1 Polo-Like
14.
J Agric Food Chem ; 61(26): 6366-75, 2013 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-23777448

RESUMO

Demethoxycurcumin (DMC), curcumin (Cur), and bisdemethoxycurcumin (BDMC) are major forms of curcuminoids found in the rhizomes of turmeric. This study examined the effects of three curcuminoid analogues on breast cancer cells. The results revealed that DMC demonstrated the most potent cytotoxic effects on breast cancer MDA-MB-231 cells. Compared with estrogen receptor (ER)-positive or HER2-overexpressing breast cancer cells, DMC demonstrated the most efficient cytotoxic effects on triple-negative breast cancer (TNBC) cells. However, nonmalignant MCF-10A cells were unaffected by DMC treatment. The study showed that DMC activated AMPK in TNBC cells. Once activated, AMPK inhibited eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) signaling and mRNA translation via mammalian target of rapamycin (mTOR) and decreased the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). DMC also targeted multiple AMPK downstream pathways. Among these, the dephosphorylation of Akt is noteworthy because it circumvents the feedback activation of Akt that results from mTOR inhibition. Moreover, DMC suppressed LPS-induced IL-6 production, thereby blocking subsequent Stat3 activation. In addition, DMC also sustained epidermal growth factor receptor (EGFR) activation by suppressing the phosphatases, PP2a and SHP-2. These results suggest that DMC is a potent AMPK activator that acts through a broad spectrum of anti-TNBC activities.


Assuntos
Anticarcinógenos/farmacologia , Carcinogênese/efeitos dos fármacos , Curcumina/análogos & derivados , Metabolismo Energético/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/química , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular Tumoral , Curcumina/farmacologia , Diarileptanoides , Ativadores de Enzimas/farmacologia , Feminino , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/prevenção & controle
15.
J Biomed Mater Res A ; 101(11): 3159-69, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23554315

RESUMO

Hair follicle transplantation is often used in the treatment of androgenetic alopecia (AGA). However, the only source of hair follicles is from human donors themselves, which limits the application of this approach. One possible solution is to reconstitute hair follicle from dissociated cells. Currently, a number of microscale technologies have been developed to create size and shape controlled microenvironments in tissue engineering. Photopolymerizable PEGDA hydrogels are often selected as promising scaffolds in engineered microtissues due to their biocompatibility and adjustable mechanical properties. Here, we fabricated an array of PEGDA microwells with center islets that mimic the architecture of human hair follicles using soft lithography. Dermal and epithelial cells were seeded in different compartments of the microstructured mould to mimic mesenchymal and epithelial compartmentalization in native hair follicles. We demonstrated that these compartmentalized microstructures support cell proliferation and cell survival over 14 days, and spreading of dermal fibroblasts was observed. This hydrogel micromould provides a potentially useful tool for engineering 3D hair follicle-mimicking complex cultures in vitro.


Assuntos
Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Engenharia Tecidual/métodos , Adulto , Contagem de Células , Derme/citologia , Dimetilpolisiloxanos/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Fenômenos Mecânicos/efeitos dos fármacos , Polietilenoglicóis , Técnicas de Cultura de Tecidos
16.
Biosens Bioelectron ; 26(10): 4124-32, 2011 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-21536420

RESUMO

This paper reports the success of amino-functionalization on multi-walled carbon nanotubes (MWCNTs) to promote neuronal cells growth on MWCNT electrode for extracellular recording, attributed to the formation of positive charge of NH(2) molecules on their surfaces. Besides, the surface of MWCNT electrode becomes hydrophilic after amino-functionalization (AF-MWCNTs) which can enhance electrical conductivity because of lower MWCNT/electrolyte interfacial impedance and higher interfacial capacitance. Durability tests show that electrical characteristics of the MWCNTs treated by 2 wt% 1,4-diaminobutane solution (2 wt%-AF-MWCNTs) can last for at least six months in air ambient. The neural recording of crayfish shows that 2 wt%-AF-MWCNTs can provide better capability on detecting action potentials of caudal photoreceptor (CPR) interneuron compared to suction glass pipette from the evidence of a higher S/N ratio (126 versus 23). The amino-functionalized MWCNT electrode is feasible for long-term recording application according to the results of biocompatibility tests. As the MWCNTs were directly synthesized on Si-based substrates by catalyst-assisted thermal chemical vapor deposition (CVD) at a low temperature (400 °C), these self-aligned MWCNT electrodes could be friendly implemented in integrated circuits fabrications.


Assuntos
Nanotubos de Carbono , Neurogênese , Potenciais de Ação , Animais , Astacoidea , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Células Cultivadas , Condutividade Elétrica , Impedância Elétrica , Técnicas Eletroquímicas , Eletrodos , Hipocampo/citologia , Técnicas In Vitro , Teste de Materiais , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Neuroglia/citologia , Neuroglia/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Espectroscopia Fotoeletrônica , Ratos
17.
J Neural Eng ; 8(3): 034001, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21474876

RESUMO

A variety of microelectrode arrays (MEAs) has been developed for monitoring intra-cortical neural activity at a high spatio-temporal resolution, opening a promising future for brain research and neural prostheses. However, most MEAs are based on metal electrodes on rigid substrates, and the intra-cortical implantation normally causes neural damage and immune responses that impede long-term recordings. This communication presents a flexible, carbon-nanotube MEA (CMEA) with integrated circuitry. The flexibility allows the electrodes to fit on the irregular surface of the brain to record electrocorticograms in a less invasive way. Carbon nanotubes (CNTs) further improve both the electrode impedance and the charge-transfer capacity by more than six times. Moreover, the CNTs are grown on the polyimide substrate directly to improve the adhesion to the substrate. With the integrated recording circuitry, the flexible CMEA is proved capable of recording the neural activity of crayfish in vitro, as well as the electrocorticogram of a rat cortex in vivo, with an improved signal-to-noise ratio. Therefore, the proposed CMEA can be employed as a less-invasive, biocompatible and reliable neuro-electronic interface for long-term usage.


Assuntos
Eletroencefalografia/instrumentação , Análise em Microsséries/instrumentação , Microeletrodos , Nanotecnologia/instrumentação , Nanotubos de Carbono/química , Animais , Astacoidea , Elasticidade , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Nanotubos de Carbono/ultraestrutura , Ratos
18.
Nanotechnology ; 21(48): 485501, 2010 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-21051797

RESUMO

To decrease the impedance of microelectrode arrays, for neuroscience applications we have fabricated and tested MEA based on multi-walled carbon nanotubes. With decreasing physical size of a microelectrode, its impedance increases and charge-transfer capability decreases. To decrease the impedance, the effective surface area of the electrode must generally be increased. We explored the effect of plasma treatment on the surface wettability of MWCNT. With a steam-plasma treatment the surface of MWCNT becomes converted from superhydrophobic to superhydrophilic; this hydrophilic property is attributed to -OH bonding on the surface of MWCNT. We reported the synthesis at 400 °C of MWCNT on nickel-titanium multilayered metal catalysts by thermal chemical vapor deposition. Applying plasma with a power less than 25 W for 10 s improved the electrochemical and biological properties, and circumvented the limitation of the surface reverting to a hydrophobic condition; a hydrophilic state is maintained for at least one month. The MEA was used to record neural signals of a lateral giant cell from an American crayfish. The response amplitude of the action potential was about 275 µV with 1 ms period; the recorded data had a ratio of signal to noise up to 40.12 dB. The improved performance of the electrode makes feasible the separation of neural signals and the recognition of their distinct shapes. With further development the rapid treatment will be useful for long-term recording applications.


Assuntos
Técnicas Eletroquímicas/instrumentação , Interações Hidrofóbicas e Hidrofílicas , Nanotubos de Carbono/química , Neurônios/fisiologia , Animais , Astacoidea/fisiologia , Espectroscopia Dielétrica , Microeletrodos , Nanotubos de Carbono/ultraestrutura , Espectroscopia Fotoeletrônica , Análise Espectral Raman , Molhabilidade
19.
Biosens Bioelectron ; 26(1): 220-7, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20685101

RESUMO

A novel cone-shaped 3D carbon nanotube (CNT) probe is proposed as an electrode for applications in neural recording. The electrode consists of CNTs synthesized on the cone-shaped Si (cs-Si) tip by catalytic thermal chemical vapor deposition (CVD). This probe exhibits a larger CNT surface area with the same footprint area and higher spatial resolution of neural recording compared to planar-type CNT electrodes. An approach to improve CNT characteristics by O(2) plasma treatment to modify the CNT surface will be also presented. Electrochemical characterization of O(2) plasma-treated 3D CNT (OT-CNT) probes revealed low impedance per unit area (∼64.5 Ω mm(-2)) at 1 kHz and high specific capacitance per unit area (∼2.5 mF cm(-2)). Furthermore, the OT-CNT probes were employed to record the neural signals of a crayfish nerve cord. Our findings suggest that OT-CNT probes have potential advantages as high spatial resolution and superb electrochemical properties which are suitable for neural recording applications.


Assuntos
Potenciais de Ação/fisiologia , Microeletrodos , Nanotubos de Carbono/química , Neurônios/fisiologia , Animais , Astacoidea , Células Cultivadas , Desenho de Equipamento , Análise de Falha de Equipamento , Conformação Molecular , Nanotubos de Carbono/ultraestrutura , Tamanho da Partícula
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