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1.
Eur J Oral Sci ; 128(2): 128-135, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32154612

RESUMO

DNA damage repair is a key factor in the maintenance of cell genome stability, plays an important role in the regulation of tumour evolution, and can affect the prognosis of cancer patients. This study aimed to detect the protein expression of the DNA damage repair protein P53 and its upstream and downstream regulators, CHK1, GADD45A, and MDM2, in oral squamous cell carcinoma (OSCC), in order to analyse the association between the expression of these proteins and overall survival, and to assess their prognostic implications for OSCC patients. The expression of the above proteins was detected by immunohistochemistry in 80 human OSCC tissue samples and in non-cancerous tissue samples. Compared to that in the non-cancerous tissue, the expression of CHK1, GADD45A, and MDM2 in OSCC tissue was significantly increased. The protein expression of the tumour suppressor gene P53 was also increased. Patients with high CHK1 and MDM2 expression levels had a reduced survival time and a poor prognosis, whereas patients with high GADD45A expression levels had a good prognosis. Our results indicate that high CHK1 expression is an independent risk factor for poor OSCC prognosis, and that CHK1 may be a potential target for OSCC clinical treatment.


Assuntos
Carcinoma de Células Escamosas , Proteínas de Ciclo Celular/genética , Quinase 1 do Ponto de Checagem/genética , Neoplasias Bucais , Proteína Supressora de Tumor p53/genética , Carcinoma de Células Escamosas/genética , DNA , Dano ao DNA , Humanos , Neoplasias Bucais/genética , Prognóstico
2.
J Cell Biochem ; 120(4): 5713-5721, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30362602

RESUMO

BACKGROUNDS AND AIMS: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blocker losartan is potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of losartan in aged patients with essential hypertension are not entirely investigated. METHODS: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. RESULTS: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared with patients without essential hypertension. Logistic regression analysis indicated that age, hypertension duration, and losartan treatment are risk factors of arterial stiffness. In a perspective study, long-term administration of losartan (50 mg/d) remarkably reduced PWV in aged patients with essential hypertension. In a longitudinal study, PWV is an independent predictor of the occurrence of acute coronary syndrome (ACS) in elderly patients with essential hypertension by using multivariate analysis. Further, the ACS occurrence was reduced by long-term administration of losartan in aged patients with essential hypertension, compared with the old hypertensive patients without taking losartan. CONCLUSION: Losartan treatment is a negative risk factor of arterial stiffness and reduces the risk of ACS in aged patients with essential hypertension.


Assuntos
Síndrome Coronariana Aguda/prevenção & controle , Anti-Hipertensivos/uso terapêutico , Hipertensão Essencial/complicações , Losartan/uso terapêutico , Análise de Onda de Pulso/métodos , Rigidez Vascular/efeitos dos fármacos , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico
3.
Gynecol Oncol ; 154(3): 583-589, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31307665

RESUMO

OBJECTIVE: To evaluate the health-related quality of life (HRQOL) in locally advanced cervical cancer (LACC) patients treated with neoadjuvant concurrent chemoradiation (CCRT) or radiation (RT) alone followed by radical surgery (RS). METHODS: In a single-center retrospective study from a prospective database, 275 FIGO Stage IB2-IIIB patients who underwent CCRT/RT + RS were included. HRQOL was prospectively assessed by EORTC QLQ-C30 and EORTC QLQ-CX24 prior to any treatment (baseline) and 6 months after surgery, respectively. RESULTS: A statistically significant and clinically relevant improvement in physical functioning (P < 0.001) and role functioning (P = 0.002, P = 0.031) was observed in patients receiving either CCRT+RS or RT + RS at follow-up. In addition, quality of life (QoL), physical functioning, and social functioning were better in the RT + RS group than the CCRT+RS group after treatment (P = 0.028, P = 0.010, P = 0.014). Symptom scores of fatigue decreased in both groups over time (P < 0.001, P = 0.004) while insomnia decreased only in the RT + RS group (P = 0.042). Worsened menopausal symptoms were documented in both groups at follow-up (P = 0.001, P = 0.047), while lymphedema was deteriorated only in patients receiving CCRT + RS (P < 0.001). Sexuality scores did not differ between groups or over time with the exception of sexual worry, which was deteriorated in patients receiving RT + RS (P = 0.042). CONCLUSIONS: QLQ-C30 functioning and tumor-related symptoms scores improved while lymphedema and menopausal symptoms worsened 6 months after neoadjuvant CCRT or RT alone followed by RS in LACC patients. Patients treated with RT + RS had a generally better HRQOL compared with those receiving CCRT+RS, though further validation with prospective randomized clinical trials is warranted.


Assuntos
Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Qualidade de Vida , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias do Colo do Útero/fisiopatologia , Neoplasias do Colo do Útero/cirurgia
4.
Sensors (Basel) ; 18(9)2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30181527

RESUMO

Generally, in order to ensure the reliability of Navigation system, vehicles are usually equipped with two or more sets of inertial navigation systems (INSs). Fusion of navigation measurement information from different sets of INSs can improve the accuracy of autonomous navigation effectively. However, due to the existence of misalignment angles, the coordinate axes of different systems are usually not in coincidence with each other absolutely, which would lead to serious problems when integrating the attitudes information. Therefore, it is necessary to precisely calibrate and compensate the misalignment angles between different systems. In this paper, a dynamic calibration method of misalignment angles between two systems was proposed. This method uses the speed and attitude information of two sets of INSs during the movement of the vehicle as measurements to dynamically calibrate the misalignment angles of two systems without additional information sources or other external measuring equipment, such as turntable. A mathematical model of misalignment angles between two INSs was established. The simulation experiment and the INSs vehicle experiments were conducted to verify the effectiveness of the method. The results show that the calibration accuracy of misalignment angles between the two sets of systems can reach to 1″ while using the proposed method.

5.
Sensors (Basel) ; 15(10): 26606-20, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26492249

RESUMO

Getting a land vehicle's accurate position, azimuth and attitude rapidly is significant for vehicle based weapons' combat effectiveness. In this paper, a new approach to acquire vehicle's accurate position and orientation is proposed. It uses biaxial optical detection platform (BODP) to aim at and lock in no less than three pre-set cooperative targets, whose accurate positions are measured beforehand. Then, it calculates the vehicle's accurate position, azimuth and attitudes by the rough position and orientation provided by vehicle based navigation systems and no less than three couples of azimuth and pitch angles measured by BODP. The proposed approach does not depend on Global Navigation Satellite System (GNSS), thus it is autonomous and difficult to interfere. Meanwhile, it only needs a rough position and orientation as algorithm's iterative initial value, consequently, it does not have high performance requirement for Inertial Navigation System (INS), odometer and other vehicle based navigation systems, even in high precise applications. This paper described the system's working procedure, presented theoretical deviation of the algorithm, and then verified its effectiveness through simulation and vehicle experiments. The simulation and experimental results indicate that the proposed approach can achieve positioning and orientation accuracy of 0.2 m and 20″ respectively in less than 3 min.

6.
J Sex Marital Ther ; 40(1): 1-16, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23656590

RESUMO

This pilot study aimed at fostering resilience among people living with HIV and improving the HIV-negative participants' acceptance of people living with HIV. A group of 75 people living with HIV who were former blood/plasma donors and 36 HIV-negative fellow villagers in rural China participated in the intervention. The 8 sessions lasted for 4 months and were facilitated by trained local family-planning officers. Efficacy of the intervention was assessed using a pre- and postprogram study design; measurements were made at baseline, at completion, and 3 months afterward completion. The authors found that the HIV-positive participants increased their levels of resilience, social support, and quality of life and that they reported fewer symptoms of depression, anxiety, and stress at the completion of the intervention; most of these changes were sustained at the 3-month follow-up. Such participants also reported subjective improvements on problem-solving skills, self-confidence, and a feeling of being cared for by others. In addition, the HIV-negative participants' discriminatory attitudes toward people living with HIV were reduced after completing the intervention. The majority of the participants was satisfied with the intervention and would recommend it to others. The train-the-trainer approach was used effectively. Positive effects of the intervention have been revealed and future randomized controlled studies are warranted.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Infecções por HIV/epidemiologia , Qualidade de Vida , Resiliência Psicológica , População Rural/estatística & dados numéricos , Adulto , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Ansiedade/psicologia , China , Comorbidade , Depressão/psicologia , Feminino , Infecções por HIV/psicologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Autoimagem , Percepção Social , Apoio Social , Adulto Jovem
7.
Sci Rep ; 14(1): 902, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195596

RESUMO

Commercial stainless steel has attracted increasing interest due to their rich content in transition metal elements and corrosion resistance properties. In this work, we design a facile and rapid route to in-situ fabricate the Cr doped FeNi layered double hydroxides nanosheets (LDHs) on modified stainless steel (Cr-FeNi LDH @ ESS) under ambient condition.The ultra small scaled 2D structure only around 20 nm diameter and metal ions with multivalent oxidation state were observed on the in situ fabricated LDHs, which provides high active area and active sites and thus promote excellent oxygen evolution reaction (OER). The Cr-FeNi LDH @ESS electrocatalysts exhibit an over potential of 280 mV at 10 mA cm-2 and achieves a Tafel slope of 44 mV dec-1 for OER in the 1.0 M KOH aqueous solution. We anticipate that the operating strategy of our system may promote the development of commercial non-precious productions as the efficient electrocatalysts for energy storage and conversion.

8.
AIDS Behav ; 17(5): 1888-94, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22802078

RESUMO

A random sample consisting of 88 sexually active people living with HIV (PLWH) and their HIV negative spouses in rural China were interviewed. Data of 68 couples (77.2 %) who gave identical responses to whether they had been using condoms consistently in the last 12 months (n = 136) were analyzed. The results showed that 27.9 % of the discordant couples used condom inconsistently in the last year. Condom non-availability was the most commonly given main reason for not using condoms. Free condoms should be made available to these low-income couples. Suicidal ideation of the PLWH and the spouse's perception on 'whether someone could contract HIV via unprotected sexual intercourse with a HIV positive person' were significantly associated with inconsistent condom use in the last year. Education program should change the cognition about the risk for HIV transmission via unprotected sex. Integrated psychological services to reduce suicidal ideation are greatly warranted.


Assuntos
Preservativos/estatística & dados numéricos , Soropositividade para HIV/psicologia , Adulto , China/epidemiologia , Escolaridade , Feminino , Soropositividade para HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Prevalência , População Rural/estatística & dados numéricos , Cônjuges/psicologia , Cônjuges/estatística & dados numéricos , Ideação Suicida , Sexo sem Proteção/psicologia , Sexo sem Proteção/estatística & dados numéricos
9.
Phys Chem Chem Phys ; 15(8): 2967-82, 2013 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-23340797

RESUMO

The dehydration mechanisms for glucose in ß-pyranose (BP) and in open-chain (OC) forms, catalyzed by acids homogeneously and heterogeneously, were investigated using density functional and two-layer ONIOM calculations. The first dehydration reaction and competing reaction pathways are the main focus of the present study. The energetics of five dehydration and two isomerization pathways were examined for the protonated form of BP in acidic aqueous solutions and the most favorable pathway of these was found to be the dehydration at the anomeric site. No dehydration pathway of OC glucose is favored over its isomerization to BP or to fructose. The relative ease of dehydration over isomerization depends on the selection of the reaction media for the protonated form of BP. These two reaction pathways catalyzed by a surface Brönsted acid site were then examined and the isomerization pathway was found to be more favorable than dehydration at the anomeric site on a surface acid site. These mechanistic insights provide an important guide for the catalyst design/selection of the reaction media for glucose dehydration.

10.
Phys Chem Chem Phys ; 15(46): 20120-33, 2013 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-24158544

RESUMO

The catalytic activity and the acrolein selectivity for liquid phase glycerol dehydration on ß zeolites (HNa-ß-k) were found to be dependent on the reaction temperature as well as on the amount of acid sites on the zeolites. An increase in the reaction temperature favors the acrolein selectivity. The acrolein selectivity increases with the Na(+)/H(+) ratio and the glycerol conversion decreases with it so that a maximum acrolein yield is obtained when a certain amount of acidic sites are replaced by non-active Na(+) sites. The computational results indicate that 3-hydoxylpropanal (HPA) is an important intermediate that determines the final product selectivity. The relative rates of the different reaction pathways for HAP can be affected by the amount of water molecules involved in its homogeneous reaction. Based on the reaction mechanism proposed, it was hypothesized that smaller pores reduce activity but increase selectivity to acrolein, and results of the H-MFI zeolite were consistent with this hypothesis. Our work provides important insight into the overall landscape of the reaction mechanism and can be used to help design reaction systems that have good acrolein selectivity for the liquid phase glycerol dehydration reactions.


Assuntos
Acroleína/química , Glicerol/química , Zeolitas/química , Ácidos/química , Catálise , Íons/química , Isomerismo , Porosidade , Teoria Quântica , Sódio/química , Temperatura , Termodinâmica
11.
Int J Oncol ; 63(2)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37350405

RESUMO

The incidence of endometrial cancer (EC) is rapidly increasing worldwide. The majority of endometrial cancers are diagnosed at an early stage and are associated with a good prognosis; however, patients with advanced­stage EC have a poor prognosis and present with invasive metastasis. The mechanisms responsible for the invasion and metastasis of endometrial cancer remain unknown. Here, the present study aimed to examine the effects of O­GlcNAcylation on the malignancy of EC and its association with Yes­associated protein (YAP). It was found that the expression of O­GlcNAc transferase (OGT) and O­GlcNAcylation were increased in EC tissues; the decrease in O­GlcNAcylation levels was found to lead to the decreased proliferation, migration and invasion of EC cells. Mass spectrometric analysis revealed that OGT knockdown reduced the O­GlcNAcylation of YAP. Furthermore, it was found that the reduction in the O­GlcNAcylation of YAP promoted its phosphorylation, which in turn inhibited the access of YAP to the nucleus and downstream target gene activation, demonstrating that the level of O­GlcNAcylation affects the development of EC. On the whole, the findings of the present study indicate that YAP is a key molecule linking the O­GlcNAcylation and Hippo pathways, which together regulate the progression of EC.


Assuntos
Neoplasias do Endométrio , Feminino , Humanos , Linhagem Celular Tumoral , Neoplasias do Endométrio/patologia , Endométrio/patologia , Via de Sinalização Hippo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proliferação de Células/fisiologia , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica
12.
Cell Physiol Biochem ; 30(2): 321-33, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22739213

RESUMO

We investigated the anti-tumor efficiency of sonodynamic therapy (SDT) on human tongue squamous carcinoma SAS cell line using low intensity ultrasound (LIU) of 0.6 and 0.8 W/cm(2), plus 5-aminolevulinic acid (ALA). Xenograft in vivo experiments using Balb/ca nude mice and MTT assays in vitro showed that ALA-LIU therapy significantly suppressed the proliferation of SAS cells. ALA-LIU therapy markedly enhanced SAS cell apoptosis rate compared to LIU alone. Based on TEM and fluorescence microscopy observations, there are notably morphology changes and seriously swollen mitochondria in xenograft tissues, and ALA-induced PpIX bond strongly to mitochondria of SAS cells. Immunohistochemical staining and western blotting demonstrated upregulation of Bax, cytochrome c and caspase-3, and downregulation of Bcl-2 for both in vivo and in vitro cases after ALA-LIU treatment. Increase of reactive oxygen species (ROS) in the ALA-LIU treatment groups were found using 2, 7-dichlorofluorescin diacetate (DCFH-DA) staining. Administration of the ROS scavenger, N-acetylcysteine (NAC), suppressed ALA-LIU-induced apoptosis and the expression of mitochondria apoptosis-related proteins, which confirmed that the ALA-LIU induced SAS cell apoptosis is through the generation of ROS. The process initially damaged mitochondria, activated pro-apoptotic factors Bax and cytochrome c and suppressed the anti-apoptotic factor Bcl-2, activated caspase-3 to executed apoptosis through mitochondrial signaling pathway.


Assuntos
Ácido Aminolevulínico/uso terapêutico , Carcinoma de Células Escamosas/terapia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Língua/terapia , Terapia por Ultrassom , Ácido Aminolevulínico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Citocromos c/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Protoporfirinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Transplante Heterólogo , Proteína X Associada a bcl-2/metabolismo
13.
Biochem Biophys Res Commun ; 400(1): 151-6, 2010 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-20709020

RESUMO

Angiogenesis is critical to a wide range of physiological and pathological processes. Scutellarin, a major flavonoid of a Chinese herbal medicine Erigeron breviscapus (Vant.) Hand. Mazz. has been shown to offer beneficial effects on cardiovascular and cerebrovascular functions. However, scutellarin's effects on angiogenesis and underlying mechanisms are not fully elucidated. Here, we studied angiogenic effects of scutellarin on human umbilical vein endothelial cells (HUVECs) in vitro. Scutellarin was found by MTT assay to induce proliferation of HUVECs. In scutellarin-treated HUVECs, a dramatic increase in migration was measured by wound healing assay; Transwell chamber assay found significantly more invading cells in scutellarin-treated groups. Scutellarin also promoted capillary-like tube formation in HUVECs on Matrigel, and significantly upregulated platelet endothelial cell adhesion molecule-1 at both mRNA and protein levels. Scutellarin's angiogenic mechanism was investigated in vitro by measuring expression of angiogenic factors associated with cell migration and invasion. Scutellarin strongly induced MMP-2 activation and mRNA expression in cultured HUVECs in a concentration-dependent manner. Taken together, these results suggest that scutellarin promotes angiogenesis and may form a basis for angiogenic therapy.


Assuntos
Indutores da Angiogênese/farmacologia , Apigenina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Glucuronatos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacos
14.
Biochem Biophys Res Commun ; 372(1): 179-85, 2008 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-18474221

RESUMO

Droperidol causes the blockage of the dopamine receptors in the central nervous system that are involved in pain transmission. However, the mechanism of action of droperidol in pain-related neurons is not clear, and it is still unknown whether opioids are involved in the modulation of this processing. The present study examines the effect of droperidol on the pain-evoked response of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the caudate nucleus (Cd) of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. Our results revealed that droperidol decreased the frequency of PEN discharge, and increased the frequency PIN discharge evoked by the noxious stimulation in the Cd of normal rats, while administration of droperidol to morphine-dependent rats produced the opposite response. Those demonstrated that droperidol is involved in the modulation of nociceptive information transmission in Cd, and there were completely opposite responses to painful stimulation between normal and morphine-dependent rats after administration of droperidol.


Assuntos
Núcleo Caudado/efeitos dos fármacos , Núcleo Caudado/fisiopatologia , Antagonistas de Dopamina/farmacologia , Droperidol/farmacologia , Dependência de Morfina/fisiopatologia , Dor/fisiopatologia , Animais , Núcleo Caudado/citologia , Eletrofisiologia , Potenciais Evocados , Feminino , Masculino , Neurônios/efeitos dos fármacos , Ratos , Ratos Wistar
15.
Oncotarget ; 8(34): 56296-56310, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915591

RESUMO

Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 µM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3.1-HER2. In MCF-10AT cells treated by 180 µM eugenol, the protein expressions of HER2, AKT, PDK1, p85, Bcl2, NF-κB, Bad and Cyclin D1 were decreased and the decreased rates were respectively 63.0%, 60.0%, 52.9%, 62.9%, 37.1%, 47.2%, 61.7%, 59.1%, while the p21, p27 and Bax expression were increased by 4.48-, 4.76- and 2.57-fold respectively. In the rat models of breast precancerous lesion, 1 mg eugenol for external use significantly inhibited the progress of breast precancerous lesion and the occurrence rate of breast precancerous lesions and invasive carcinomas was decreased by about 30.5%. Furthermore eugenol for external (1 mg) markedly decreased the protein expressions of HER2 (62.9%), AKT (58.6%), PDK1 (56.4%), p85 (54.3%), Bcl2 (59.3%), NF-κB (65.7%), Bad (64.0%), Cyclin D1 (43.0%), while p21, p27 and Bax protein expressions were respectively increased 1.83-, 2.52- and 2.51-fold. The results showed eugenol could significantly inhibit the development of breast precancerous lesions by blocking HER2/PI3K-AKT signaling network. So eugenol may be a promising external drug for breast precancerous lesions.

16.
Sci Rep ; 7(1): 12920, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-29018241

RESUMO

Alteration in cellular energy metabolism plays a critical role in the development and progression of cancer. Targeting metabolic pathways for cancer treatment has been investigated as potential preventive or therapeutic methods. Eugenol (Eu), a major volatile constituent of clove essential oil mainly obtained from Syzygium, has been reported as a potential chemopreventive drug. However, the mechanism by which Eu regulates cellular energy metabolism is still not well defined. This study was designed to determine the effect of Eu on cellular energy metabolism during early cancer progression employing untransformed and H-ras oncogene transfected MCF10A human breast epithelial cells. Eu showed dose-dependent selective cytotoxicity toward MCF10A-ras cells but exhibited no apparent cytotoxicity in MCF10A cells. Treatment with Eu also significantly reduced intracellular ATP levels in MCF10A-ras cells but not in MCF10A cells. This effect was mediated mainly through inhibiting oxidative phosphorylation (OXPHOS) complexs and the expression of fatty acid oxidation (FAO) proteins including PPARα, MCAD and CPT1C by downregulating c-Myc/PGC-1ß/ERRα pathway and decreasing oxidative stress in MCF10A-ras cells. These results indicate a novel mechanism involving the regulation of cellular energy metabolism by which Eu may prevent breast cancer progression.


Assuntos
Proteínas de Transporte/metabolismo , Regulação para Baixo/efeitos dos fármacos , Eugenol/farmacologia , Ácidos Graxos/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores de Estrogênio/metabolismo , Proteínas ras/metabolismo , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Modelos Biológicos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Ligação a RNA , Transdução de Sinais/efeitos dos fármacos , Receptor ERRalfa Relacionado ao Estrogênio
17.
Sci Rep ; 7: 40967, 2017 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-28102324

RESUMO

Sonodynamic therapy (SDT) is an innovative modality for cancer treatment. But the biological effect of SDT on oral squamous cell carcinoma has not been studied. Our previous study has shown that endo-Protoporphyrin IX based SDT (ALA-SDT) could induce apoptosis in human tongue squamous carcinoma SAS cells through mitochondrial pathway. Herein, we investigated the effect of exo- Protoporphyrin based SDT (PpIX-SDT) on SAS cells in vitro and in vivo. We demonstrated that PpIX-SDT increased the ratio of cells in the G2/M phase and induced 3-4 times more cell apoptosis compared to sonocation alone. PpIX-SDT caused cell membrane damage prior to mitochondria damage and upregulated the expression of Fas and Fas L, while the effect was suppressed if cells were pre-treated with p53 inhibitor. Additionally, we examined the SDT-induced cell apoptosis in two cell lines with different p53 status. The increases of p53 expression and apoptosis rate in wild-type p53 SAS cells were found in the SDT group, while p53-mutated HSC-3 cells did not show such increase. Our data suggest that PpIX-SDT suppress the proliferation of SAS cells via arresting cell cycle at G2/M phase and activating the extrinsic Fas-mediated membrane receptor pathway to induce apoptosis, which is regulated by p53.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma de Células Escamosas/terapia , Neoplasias Bucais/terapia , Fármacos Fotossensibilizantes/farmacologia , Protoporfirinas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Transplante de Neoplasias , Fármacos Fotossensibilizantes/administração & dosagem , Protoporfirinas/administração & dosagem , Sonicação/métodos , Resultado do Tratamento , Células Tumorais Cultivadas
18.
Sci Rep ; 6: 24905, 2016 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-27125313

RESUMO

Stress is increasingly present in everyday life in our fast-paced society and involved in the pathogenesis of many psychiatric diseases. Corticotrophin-releasing-hormone (CRH) plays a pivotal role in regulating the stress responses. The tree shrews are highly vulnerable to stress which makes them the promising animal models for studying stress responses. However, the mechanisms underlying their high stress-susceptibility remained unknown. Here we confirmed that cortisol was the dominate corticosteroid in tree shrew and was significantly increased after acute stress. Our study showed that the function of tree shrew CRH - hypothalamic-pituitary-adrenal (HPA) axis was nearly identical to human that contributed little to their hyper-responsiveness to stress. Using CRH transcriptional regulation analysis we discovered a peculiar active glucocorticoid receptor response element (aGRE) site within the tree shrew CRH promoter, which continued to recruit co-activators including SRC-1 (steroid receptor co-activator-1) to promote CRH transcription under basal or forskolin/dexamethasone treatment conditions. Basal CRH mRNA increased when the aGRE was knocked into the CRH promoter in human HeLa cells using CAS9/CRISPR. The aGRE functioned critically to form the "Stress promoter" that contributed to the higher CRH expression and susceptibility to stress. These findings implicated novel molecular bases of the stress-related diseases in specific populations.


Assuntos
Hidrocortisona/metabolismo , Regiões Promotoras Genéticas , Elementos de Resposta , Estresse Fisiológico , Tupaiidae/fisiologia , Animais , Hormônio Liberador da Corticotropina/biossíntese , Perfilação da Expressão Gênica , Técnicas de Introdução de Genes , Células HeLa , Humanos , Transcrição Gênica
19.
Mol Med Rep ; 12(2): 3177-83, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25955510

RESUMO

Sonodynamic therapy (SDT) with 5-aminolevulinic acid (5-ALA) can effectively inhibit various types of tumor in vitro and in vivo. However, the association between the efficacy of SDT and the phase of the cell cycle remains to be elucidated. 5-ALA may generate different quantities of sonosensitizer, protoporphyrin IX (PpIX), in different phases of the cell cycle, which may result in differences in sensitivity to 5-ALA-induced SDT. The present study aimed to investigate the effect of the cell cycle on the susceptibility of SAS cells to SDT following synchronization to different cell cycle phases. These results indicates that the rates of cell death and apoptosis of the SAS cells in the S and G2/M phases were significantly higher following SDT, compared with those in the G1-phase cells and unsynchronized cells, with a corresponding increase in PpIX in the S and G2/M cells. In addition, the expression of caspase-3 increased, while that of B-cell lymphoma (Bcl)-2 decreased markedly in theS and G2/M cells following SDT. Cyclin A was also expressed at higher levels in the S and G2/M cells, compared with the G1-phase cells. SDT also caused a significant upregulation of cyclin A in all phases of the cell cycle, however this was most marked in the S and G2/M cells. It was hypothesized that high expression levels of cyclin A in the S and G2/M cells may promote the induction of caspase-3 and reduce the induction of Bcl-2 by SDT and, therefore, enhance apoptosis. Taken together, these data demonstrated that cells in The S and G2/M phases generate more intracellular PpIX, have higher levels of cyclin A and are, therefore, more sensitive to SDT-induced cytotoxicity. These findings indicate the potential novel approach to preventing the onset of cancer by combining cell-cycle regulators with SDT. This sequential combination therapy may be a simple and cost-effective way of enhancing the effects of SDT in clinical settings.


Assuntos
Ácido Aminolevulínico/farmacologia , Ciclo Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Fármacos Fotossensibilizantes/farmacologia , Biotransformação , Caspase 3/genética , Caspase 3/metabolismo , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Ciclina A/genética , Ciclina A/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Epiteliais/efeitos da radiação , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Protoporfirinas/biossíntese , Tolerância a Radiação , Transdução de Sinais , Língua/efeitos dos fármacos , Língua/metabolismo , Língua/patologia , Língua/efeitos da radiação , Terapia por Ultrassom/métodos , Ondas Ultrassônicas
20.
Sci Rep ; 5: 16291, 2015 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-26573407

RESUMO

Element doping is commonly used to adjust the carrier concentrations in semiconductors such as thermoelectric materials. However, the doping process unavoidably brings in defects or distortions in crystal lattices, which further strongly affects the physical properties of the materials. In this work, high energy photons have been used to activate the carriers in Cu2S thermoelectric films. As a result, the carrier concentrations, and the respective electrical conductivity as well as Seebeck coefficient are further changed. The photon-induced electrical transport properties are further analyzed utilizing a Parallel circuit model. Due to the realization of optimized carrier concentrations by photon activation, the power factor of Cu2S film is improved more than 900 times as compared with the dark data. As compared to the traditional doping process, the approach using photon activation can realize the tuning of carrier concentrations without affecting crystal lattice. This method provides an opportunity to investigate the intrinsic physical properties of semiconductor materials without involving traditional element doping process that usually brings in additional lattice defects or distortions.

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