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1.
Cell Signal ; 106: 110628, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36774973

RESUMO

Hepatocellular carcinoma (HCC) is the sixth most frequent human cancer and the world's third most significant cause of cancer mortality. HCC treatment has recently improved, but its mortality continues to increase worldwide due to its extremely complicated and heterogeneous genetic abnormalities. After nitric oxide (NO) and carbon monoxide (CO), the third gas signaling molecule discovered is hydrogen sulfide (H2S), which has long been thought to be a toxic gas. However, numerous studies have proven that H2S plays many pathophysiological roles in mammals. Endogenous or exogenous H2S can decrease cell proliferation, promote apoptosis, block cell cycle, invasion and migration through various cellular signaling pathways. This review analyzes and discusses the recent literature on the function and molecular mechanism of H2S and H2S donors in HCC, so as to provide convenience for the scientific research and clinical application of H2S in the treatment of liver cancer.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Sulfeto de Hidrogênio , Neoplasias Hepáticas , Animais , Humanos , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Sulfeto de Hidrogênio/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Transdução de Sinais/fisiologia , Óxido Nítrico/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Mamíferos/metabolismo
2.
Br J Ophthalmol ; 107(5): 677-682, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-34933895

RESUMO

PURPOSE: To describe the prevalence and risk factors of primary angle-closure glaucoma (PACG) and to explore nationality difference in Chinese. METHODS: The Yunnan Minority Eye Study was conducted in a rural multiethnic area in Yunnan province and included 6546 participants aged over 50 years. PACG was diagnosed based on International Society of Geographical and Epidemiologic Ophthalmology criteria by experienced ophthalmologists. Multivariate regression modelling was conducted to examine risk factors for PACG. Principal component analyis (PCA) was performed to evaluate the effects of ethnicity on PACG. RESULTS: The overall prevalence of PACG was 0.7% (95% CIs: 0.5% to 0.9%). PCA indicated that ethnicity is significantly related to the presence of PACG (p<0.001) after controlling for other risk factors. In addition, higher PACG prevalence was also correlated with older age (60-69 years group (OR: 3.47; 95% CI: 1.11 to 10.84; p<0.05) and 70-79 years group (OR: 4.71; 95% CI: 1.40 to 15.86; p<0.05) as compared with 50-59 years group), higher intraocular pressures (OR: 1.26; 95% CI: 1.17 to 1.36; p<0.001), shorter axial lengths (OR: 0.42; 95% CI: 0.32 to 0.56; p<0.001) and thinner central corneal thicknesses (OR: 0.89; 95% CI: 0.81 to 0.99; p<0.05). CONCLUSIONS: This multiethnic study on Chinese adults living in the same geographical location indicated that ethnicity is a significant risk factor for PACG. However, there were still some of the effects of ethnic differences on the prevalence of PACG that could not be explained and further studies should take culture and lifestyle factors into account.


Assuntos
Glaucoma de Ângulo Fechado , Adulto , Humanos , Pessoa de Meia-Idade , Glaucoma de Ângulo Fechado/epidemiologia , Glaucoma de Ângulo Fechado/diagnóstico , Pressão Intraocular , Prevalência , População do Leste Asiático , Estudos Transversais , População Rural , Distribuição por Idade , China/epidemiologia , Fatores de Risco
3.
BMC Ophthalmol ; 22(1): 95, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227222

RESUMO

BACKGROUND: To investigate the level of knowledge, attitude, and practices about glaucoma and associated factors among primary glaucoma patients in Kunming, China. METHODS: A hospital-based study was conducted on 93 patients from the First Affiliated Hospital of Kunming Medical University. Interviewer-administered questionnaires were used to collect data after written informed consent. Data were analyzed by SPSS 19.0. Univariate and multivariate logistic regression models were used to identify factors. A Chi-square test was used to analyze the association between knowledge of glaucoma and medication compliance, Mann-Whitney U test was performed to assess the relationship between knowledge of glaucoma and quality of life in patients with glaucoma. P-value < 0.05 was considered statistically significant. RESULTS: Among 93 patients, 55 (59.14%) were aware of glaucoma, 48 (51.61%) had good knowledge of glaucoma, while 45 (48.39%) had poor knowledge. Younger age and duration of glaucoma were associated positively with knowledge of glaucoma. 87 (93.54%) patients got knowledge of their disease from doctors. 79.17% of respondents could use all the anti-glaucoma medications on time, out of which 54.17% had good knowledge of glaucoma while 25.00% had poor knowledge of glaucoma. 30.56% of respondents used to stop anti-glaucoma medications on their own out of which only 9.72% had good knowledge of glaucoma while 20.83% had poor knowledge of glaucoma. Patients with good knowledge of glaucoma had lower scores on the Glaucoma Quality of Life-15 questionnaire. Thus, the compliance to anti-glaucoma medications and glaucoma-related quality of life were better in patients with good knowledge. CONCLUSIONS: The level of knowledge of glaucoma among patients in Kunming is relatively low. Improving knowledge with suitable content for patients through effective multiple means such as the mass media rather than relying only on ophthalmologists may be a veritable first step in combating blindness from glaucoma and enhancing patients' quality of life.


Assuntos
Glaucoma , Qualidade de Vida , Glaucoma/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Adesão à Medicação , Inquéritos e Questionários
4.
Int J Ophthalmol ; 14(8): 1185-1191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414082

RESUMO

AIM: To compare visual field defects using the Swedish Interactive Thresholding Algorithm (SITA) Fast strategy with SITA Faster strategy, a newly developed time-saving threshold visual field strategy. METHODS: Ninety-three participants (60 glaucoma patients and 33 normal controls) were enrolled. One eye from each participant was selected randomly for the study. SITA Fast and SITA Faster were performed using the 24-2 default mode for each test. The differences of visual field defects between the two strategies were compared using the test duration, false-positive response errors, mean deviation (MD), visual field index (VFI) and the numbers of depressed test points at the significant levels of P<5%, <2%, <1%, and <0.5% in probability plots. The correlation between strategies was analyzed. The agreement between strategies was acquired by Bland-Altman analysis. RESULTS: Mean test durations were 246.0±60.9s for SITA Fast, and 156.3±46.3s for SITA Faster (P<0.001). The test duration of SITA Faster was 36.5% shorter than SITA Fast. The MD, VFI and numbers of depressed points at P<5%, <2%, <1%, and <0.5% in probability plots showed no statistically significant difference between two strategies (P>0.05). Correlation analysis showed a high correlation for MD (r=0.986, P<0.001) and VFI (r=0.986, P<0.001) between the two strategies. Bland-Altman analysis showed great agreement between the two strategies. CONCLUSION: SITA Faster, which saves considerable test time, has a great test quality comparing to SITA Fast, but may be not directly interchangeable.

5.
Int J Ophthalmol ; 13(4): 580-586, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32399408

RESUMO

AIM: To investigate the effects of intraocular lens (IOL) implantation on visual field (VF) in patients with glaucoma and comorbid cataracts (G&C) with different disease severities. METHODS: Totally 56 eyes of 50 patients with primary G&C were included. All patients were divided into three groups based on the severity of the VF defect: the mild, moderate, and severe stage. Phacoemulsification was performed for cataract removal combined with IOL implantation. Visual acuity (VA) and VF tests were performed for all enrolled patients, up to 3mo after surgery. Changes in VF threshold and global VF index in various groups were also recorded before and after surgery. The mean light sensitivity (MS) values and the changes following surgery (DMS) were compared between the three groups. Advanced Glaucoma Intervention Study (AGIS) scoring was analyzed on all VF results for analysis of changes in VF before and after surgery. RESULTS: Following surgery, the MS values of the three groups of G&C increased significantly, while the AGIS scores decreased statistically in all groups. The DMS values for the three zones in moderate and severe stage but not mild stage were statistically different between zones. The DMS value was significantly higher in zone I than those in zone II and III (zone I>zone II>zone III; P<0.05). The DMS was significantly higher in zone I than that in zone III in moderate stage patients (zone I>zone II>zone III; P<0.01), while the DMS values in the severe stage patients was significantly higher in zone I than those in zone II and III (zone I>zone II>zone III; P<0.01). CONCLUSION: The mean VF sensitivity of glaucoma patients increased significantly after cataract removal and IOL implantation. Variations in the severity and distribution of characteristics of VF defects result in differences in postoperative VF improvements after cataract surgery. The magnitude of increase in VF sensitivity is associated with VF defect characteristic in glaucoma.

6.
Int J Ophthalmol ; 12(7): 1075-1082, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341795

RESUMO

AIM: To determine the effect of pirfenidone on the activated human Müller cells by platelet-derived growth factor-BB (PDGF-BB). METHODS: The primary human Müller cells were separated from retinal tissues and established the pathogenic model by stimulated with PDGF-BB. The Müller cells behaviour of normal group and the model group was measured by MTT assay, Trypan blue assay, cell migration assay, and collagen contraction assay. The expression of transforming growth factor (TGF)-ß1, -ß2, and pigment epithelium-derived factor (PEDF) was estimated with real-time polymerase chain reaction (PCR), Western blot and immunofluorescence analyses. RESULTS: A pathogenic/proliferative model of Müller cells was established by stimulating normal cultured Müller cells with 10 ng/mL PDGF-BB for 48h. After treated with 0.2 and 0.3 mg/mL pirfenidone, the proliferation, migration and collagen contraction was statistically significantly depressed in the model group compared with the normal groups. The expression levels of TGF-ß1 and TGF-ß2 were significantly down-regulated, while the PEDF expression was significantly up-regulated after treated with 0.2 and 0.3 mg/mL pirfenidone in the model group. CONCLUSION: Pirfenidone effectively suppress the proliferation, migration and collagen contraction of the human Müller cells stimulated with PDGF-BB through down-regulation of TGF-ß1/TGF-ß2 and up-regulation of PEDF.

7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(1): 83-87, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31037910

RESUMO

OBJECTIVE: To determine the associations of pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with gestational diabetes mellitus (GDM). METHODS: A prospective cohort of pregnant women were screened for GDM at 24-28 weeks of gestation between 2013 and 2015, resulting in a sample of 3 593 with GDM and 15 346 without GDM. The body mass, plasma glucose, and height data of the participants were collected by the local medical workers. Multivariate logistic regression analyses were performed to determine the associations of pre pregnancy body mass index and weight gain during pregnancy with GDM. RESULTS: The participants with pre pregnancy overweight [odds ratio(OR)=2.44, 95% cofidence interval(CI)1.98-2.99] and obesity (OR=4.98, 95%CI 2.52-9.91) were more likely to develop GDM. According to the Institute of Medicine (IOM) criteria, excessive GWG in the first trimester occurred in 8.46% of the women, compared with 55.07% in the second trimester. After adjustment for age at delivery and pre pregnancy BMI, high GWG in the first trimesters in advanced maternal age (age at delivery≥35 yr.) group (OR=1.42, 95%CI 1.02-2.28) was a risk factor for GDM while the OR value of the non-advanced maternal age (age at delivery≤35 yr.) group was not statistically significant. In second trimesters, both advanced maternal age group (OR=1.59, 95%CI 1.14-1.88) and non-advanced maternal age group (OR=1.49, 95%CI 1.20-1.72) in high GWG were associated with high risk of GDM. CONCLUSION: Pre pregnancy overweight and obesity and excessive GWG during early and second trimesters of pregnancy may increase the risk of GDM in women in Southwestern China.


Assuntos
Diabetes Gestacional , Índice de Massa Corporal , China , Feminino , Ganho de Peso na Gestação , Humanos , Gravidez , Estudos Prospectivos
8.
Sci Rep ; 7(1): 635, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28377573

RESUMO

Corythucha ciliata (Say), an invasive pest originating from North America, causes severe damage on sycamore trees. However, little is known about the population genetics and evolutionary forces underlying the invasiveness of this important pest. In the present study, we use three mitochondrial genes (COI, ND1 and ND5) and nine microsatellite markers to investigate the population genetics of C. ciliata and retrace its spread through China. The results suggest a low level of genetic diversity in Chinese and European populations of C. ciliata. Our results indicate that populations of C. ciliata have obvious genetic structure, and genetic differentiation is not caused by geographic isolation. In median-joining networks, we observed a higher frequency of shared haplotypes in groups 1 and 3. Based on gene flow and approximate Bayesian computation analyses, we discovered that C. ciliata first invaded the east coast of China and subsequently moved inland. Demographic analysis suggested that populations of C. ciliata in China may have undergone a recent bottleneck effect. Finally, our results suggest that population structure, high gene flow and environmental conditions have favored the broad invasiveness of this important pest.


Assuntos
Estruturas Genéticas , Genética Populacional , Heterópteros/genética , Animais , Teorema de Bayes , China , DNA Mitocondrial , Evolução Molecular , Fluxo Gênico , Variação Genética , Haplótipos , Heterópteros/classificação , Espécies Introduzidas , Repetições de Microssatélites , Filogenia , Dinâmica Populacional
9.
Am J Ophthalmol ; 176: 127-133, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28104416

RESUMO

PURPOSE: The prevalence of primary open-angle glaucoma (POAG) in China has been reported previously, and was lower than that in white and black populations. However, the incidence of POAG in China has not been reported. Therefore, a longitudinal study was conducted to determine the 5-year cumulative incidence and predictors of POAG in China. DESIGN: Population-based cohort study. METHODS: A total of 1520 participants (71.3% of the subjects in the baseline survey) of Bai ethnicity were examined and followed for 5 years. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology Classification criteria. Multivariable logistic regression models were fitted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 19 new cases of POAG were detected. The 5-year cumulative incidence of POAG was 1.3% (95% CI, 0.7-1.9). In multivariate analyses, incident POAG was associated with baseline variables including increased age (OR, 4.3; 95% CI, 1.4-13.8; P = .02; 70 years or older vs 50-59 years), elevated IOP (OR, 3.5; 95% CI, 2.0-5.9; P < .001; per 10 mm Hg increase), lower education level (OR, 0.3; 95% CI, 0.1-0.8; P = .02; post-primary education vs no formal education), and the presence of myopia (OR, 3.4; 95% CI, 1.3-8.6; P < .01). CONCLUSIONS: The average annual incidence of POAG in Bai Chinese was lower than that in populations of African descent and white race. The results are important to elucidate the racial/ethnic difference in POAG incidence and for the clinical management and health resource allocation in China.


Assuntos
Etnicidade , Glaucoma de Ângulo Aberto/etnologia , Vigilância da População/métodos , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Intervalos de Confiança , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Tempo
10.
Sci Rep ; 6: 22590, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26932265

RESUMO

Dai ethnicity is one of the major Chinese ethnic minorities with a population of about 1.2 million. We aimed to determine the prevalence and potential causes of visual impairment (VI) among ethnic Dai adults aged 50 years or older in a rural community in China. A population-based survey including 2163 ethnic Dai people (80.5%) was undertaken using a random cluster sampling strategy. The detailed eye examination was performed after pupil dilation by trained study ophthalmologists and optometrists. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study logMAR chart and VI was defined as a VA of less than 20/63 in the better-seeing eye. The overall prevalence of presenting blindness and low vision was 3.0% (95% CI, 2.3-3.7) and 13.3% (95% CI, 11.9-14.8), respectively. The prevalence estimates were reduced to 2.1% (95% CI, 1.5-2.8) and 6.7% (95% CI, 5.7-7.8) when BCVA was considered. Men were more likely to be affected by low vision but less likely to be blind compared with women. Cataract accounted for 62.7% of presenting low vision and 68.8% of presenting blindness, respectively. In conclusion, VI was a significant health concern in Dai Chinese in China.


Assuntos
População Rural , Transtornos da Visão/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Visão/fisiopatologia , Acuidade Visual
11.
J Hazard Mater ; 292: 126-36, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25814184

RESUMO

Facets coupled BiOBr with amorphous TiO2 composite photocatalysts are synthesized via an in situ direct growth approach under microwave irradiation. XRD, SEM and HRTEM characterizations indicate that the heterointerface between BiOBr and amorphous TiO2 occurs mainly on the {001} facets of BiOBr. BET and TEM verify that the heterojunctions possess higher specific surface areas and smaller amorphous TiO2 particle size than bare BiOBr and amorphous TiO2, exhibiting the inhibition function of BiOBr on the growth of TiO2 particles. XPS verifies the interaction between the two components. The degradation of methyl orange (MO) and phenol are used as the objective reaction to evaluate the photocatalytic activity of the as-prepared samples. The reaction rate constant of 15% TiO2/BiOBr composite is 3.4 times greater than that of pure BiOBr, which is attributed to its higher surface area, and efficient separation of photo-generated electron-hole pairs between BiOBr and amorphous TiO2.


Assuntos
Bismuto/química , Titânio/química , Catálise , Microscopia Eletrônica de Varredura , Processos Fotoquímicos , Difração de Raios X
12.
J Cancer Res Ther ; 10 Suppl: 240-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25693927

RESUMO

Epigenetics play important roles during development progress of tumor. The histone modifications are the most important constituted field. Recently, accumulating research focused on exploring the roles of those modifications in regulating tumorigenesis. Moreover, the dysregulation of histone modifications is supposed to have vital clinical significance. Numerous histone modifications have the potential to be prognostic biomarkers, monitoring response of therapy, early diagnostic markers. Herein, we review the recent advances of histone modifications involving development of gastric cancer.


Assuntos
Biomarcadores Tumorais/genética , Epigênese Genética/genética , Histonas/genética , Neoplasias Gástricas/genética , Animais , Transformação Celular Neoplásica/genética , Humanos
13.
Ying Yong Sheng Tai Xue Bao ; 25(12): 3637-44, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25876418

RESUMO

With the urban eco-environment increasingly deteriorating, the ecosystem services provided by modern urban agriculture are exceedingly significant to maintain and build more suitable environment in a city. Taking Xi' an metropolitan as the study area, based on remote sensing data, DEM data and the economic and social statistics data, the water and soil conservation service of the agricultural ecosystems was valued employing the remote sensing and geographic information system method, covering the reduction values on land waste, soil fertility loss and sediment loss from 2000 to 2011, and analyzed its changes in time and space. The results showed that during the study period, the total value of water and soil conservation service provided by agricultural systems in Xi' an metropolitan was increased by 46,086 and 33.008 billion yuan respectively from period of 2000 to 2005 and from 2005 to 2011. The cultivated land (including grains, vegetables and other farming land), forest (including orchard) and grassland provided higher value on the water and soil conservation service than waters and other land use. Ecosystem service value of water and soil conserva- tion provided by agriculture was gradually decreasing from the southern to the northern in Xi' an metropolitan. There were significantly positive relationship between the ecosystem service value and the vegetation coverage. Forest, orchard and grassland distributed intensively in the southern which had higher vegetation coverage than in northern where covered by more cultivated land, sparse forest and scattered orchard. There were significantly negative correlation between the urbanization level and the value of water and soil conservation. The higher level of urbanization, the lower value there was from built-up area to suburban and to countryside within Xi' an metropolitan.


Assuntos
Agricultura , Conservação dos Recursos Naturais , Solo , Água , China , Cidades , Ecossistema , Monitoramento Ambiental , Sistemas de Informação Geográfica , Urbanização
14.
Sci Rep ; 3: 2342, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23907561

RESUMO

The mechanisms underlying the retention of inorganic N in acidic forest soils in southern China are not well understood. Here, we simultaneously quantified the gross N transformation rates of various subtropical acidic forest soils located in southern China (southern soil) and those of temperate forest soils located in northern China (northern soil). We found that acidic southern soils had significantly higher gross rates of N mineralization and significantly higher turnover rates but a much greater capacity for retaining inorganic N than northern soils. The rates of autotrophic nitrification and NH3 volatilization in acidic southern soils were significantly lower due to low soil pH. Meanwhile, the relatively higher rates of NO3(-) immobilization into organic N in southern soils can counteract the effects of leaching, runoff, and denitrification. Taken together, these processes are responsible for the N enrichment of the humid subtropical forest soils in southern China.


Assuntos
Compostos Inorgânicos/química , Compostos de Nitrogênio/química , Solo/química , Árvores/química , China , Concentração de Íons de Hidrogênio
15.
Scand J Urol ; 47(2): 118-21, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22839104

RESUMO

UNLABELLED: OBJECTIVE.The aim of this study was to report the authors' experience with percutaneous intrarenal marsupialization of symptomatic peripelvic renal cysts. MATERIAL AND METHODS: Thirty-one patients (16 male and 15 female, with a mean age of 49 years) with a peripelvic renal cyst associated with chronic flank or lumbar pain or urinary infection were selected for percutaneous intrarenal marsupialization with a 2 µm laser in the authors' centre from January 2005 to December 2010. Cyst size ranged from 4.5 to 10.5 (mean 6.0) cm. The cysts were punctured by a percutaneous technique guided by ultrasonography, a 20.8 F nephroscope was introduced and the whole internal surface of the cyst was inspected. Methylene blue was injected through the ureteral catheter to help identify the collecting system. A 1.5-4 cm incision was made at the avascular area of the cystic wall by the 2 µm laser to achieve intrarenal marsupialization of the cyst into the renal collecting system. One or two 6 F double-J stents were placed with the proximal end in the cyst for 2-3 months. RESULTS: The mean operation time was 50 (25-120) min. No serious complications such as massive bleeding, urine leak or infected haematoma occurred. The patients were followed up for a mean of 12 (range 3-36) months. All patients were relieved of their symptoms. Eighteen cysts disappeared after surgery, while 13 cysts reduced in size by over one-third and communicated with the renal collecting system. No enlargement of cysts was observed. CONCLUSIONS: Percutaneous intrarenal marsupialization with a 2 µm laser is an effective and safe procedure and may offer a minimally invasive alternative for the management of symptomatic peripelvic renal cysts.


Assuntos
Doenças Renais Císticas/cirurgia , Pelve Renal/cirurgia , Laparoscopia/métodos , Terapia a Laser/métodos , Adulto , Idoso , China , Feminino , Seguimentos , Humanos , Doenças Renais Císticas/diagnóstico por imagem , Pelve Renal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
16.
Ann Surg Oncol ; 18(2): 580-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20803081

RESUMO

BACKGROUND: Inhibition of mammalian target of rapamycin (mTOR) represents an attractive target for anticancer therapy, but its role in suppression of colorectal cancer (CRC) cell growth by cyclooxygenase-2 (COX-2) inhibitors is unclear. Here, we analyzed the effect of indomethacin (Indo, a nonselective COX-2 inhibitor) and nimesulide (Nim, a selective COX-2 inhibitor) on mTOR signaling in CRC cells in vitro and in vivo to determine the dependence of this effect on COX-2. METHODS: Human CRC cell lines with varying COX-2 expression levels were treated with Indo and Nim. Western blot test was performed to detect mTOR-related components (mTOR, p70s6 K, and 4EBP1), and cell viability, cell cycle, and apoptosis were assessed. HCT116 and SW1116 cells were injected into athymic nude mice to establish a CRC xenograft model. After treatment with Nim, tumor volume, mTOR signaling, and apoptosis were evaluated in this model. HT29 and SW1116 cells were also treated with Nim after transfection with COX-2-specific small interfering RNA (siRNA) to assess dependence of COX-2 on mTOR signaling under drug treatment. RESULTS: Both Indo and Nim reduced mTOR signaling activity in CRC cells that differ in their COX-2 expression in vitro and in vivo. Additionally, Indo and Nim could reduce the mTOR signaling activity after COX-2 silencing in CRC cells. CONCLUSIONS: mTOR signaling is involved in Indo- and Nim-mediated suppression of CRC growth via a COX-2 independent pathway. This study unveils a novel mechanism through which COX-2 inhibitors exerts their anticancer effects and further emphasizes targeting mTOR signaling in anticancer therapy.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/química , Indometacina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/genética , Células Tumorais Cultivadas
17.
Dig Dis Sci ; 55(11): 3138-46, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20127415

RESUMO

BACKGROUND AND AIMS: The function of human macrophage metalloelastase (HME) also known as matrix metalloproteinase 12, in tumorigenesis is contradictory. The current study was designed to investigate the association of HME expression with angiogenesis and prognosis of gastric carcinomas. METHODS: In situ hybridization and immunohistochemistry were used to detect HME in human gastric carcinomas, chronic gastritis with atypical hyperplasia, and normal gastric epithelium mucosa. The results were further confirmed by RT-PCR or semi-quantitative reverse transcription polymerase chain reaction and Western blotting in gastric carcinomas and paired noncancerous tissues. VEGF and microvessel density count were also detected by immunohistochemical staining in all carcinoma tissues. The prognostic significance of HME was assessed with multiple linear regression analysis and Cox proportional hazards model. RESULTS: High expression of HME protein/mRNA was observed in gastric carcinomas and atypical hyperplasia tissues compared with normal gastric epithelium mucosa, or paired noncancerous tissues. HME protein/mRNA were negatively correlated with MVD (p < 0.01), VEGF (p < 0.01), tumor differentiation grade (p < 0.05), vascular invasion (p < 0.01), and recurrence (p < 0.05-0.01). HME protein was an independent influential factor of MVD (p < 0.01). HME protein/mRNA was an independent prognostic factor of gastric carcinoma (p < 0.05-0.01). Patients with overexpression of HME protein/mRNA demonstrated a significantly better survival rate compared with those who did not (p < 0.05-0.01). CONCLUSIONS: Overexpression of HME is strongly correlated with the reduced angiogenesis and vascular invasion of gastric carcinoma, and may serve as a useful predictive indicator in patients with this disease.


Assuntos
Gastrite/metabolismo , Metaloproteinase 12 da Matriz/metabolismo , Neovascularização Patológica/enzimologia , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Western Blotting , Doença Crônica , Progressão da Doença , Feminino , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
18.
Braz. j. microbiol ; 40(2): 373-379, Apr.-June 2009. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-520226

RESUMO

A lipopeptide biosurfactant produced by Bacillus natto TK-1 has a strong surface activity. The biosurfactant was found to be an anti-adhesive agent against several bacterial strains, and also showed a broad spectrum of antimicrobial activity. The biosurfactant induced a significant reduction in tumor cells viability in a dose- dependent manner.


Um lipopeptídio biosurfactante produzido por Bacillus natto TK-1 apresenta intensa atividade de superfície. Verificou-se que o biosurfactante apresentou atividade antiadesiva contra várias cepas bacterianas, e também atividade antimicrobiana de amplo espectro. O biosurfactante causou uma redução significativa na viabilidade de células tumorais, de forma dose-dependente.


Assuntos
Humanos , Bacillus subtilis , Peptídeos/análise , Células Tumorais Cultivadas , Métodos , Métodos
19.
Biotechnol Appl Biochem ; 52(Pt 2): 97-106, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18197839

RESUMO

An antitumour lipopeptide biosurfactant purified from Bacillus natto TK-1 was able to inhibit the proliferation of MCF-7 human breast-cancer cells in a dose- and time-dependent manner. The activity of lactate dehydrogenase release showed no significant difference between MCF-7 cells treated with lipopeptide and untreated controls. The antitumour activity of the lipopeptide in MCF-7 cells was associated with cell apoptosis determined by typical morphological changes and sub-G(1) peak in cell growth-phase distribution. The cell cycle was arrested at G(2)/M phase. In addition, the caspase activity assay revealed that lipopeptide-induced apoptosis in MCF-7 cells was associated with caspase 3.


Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Bacillus/metabolismo , Lipopeptídeos/isolamento & purificação , Lipopeptídeos/farmacologia , Tensoativos/isolamento & purificação , Tensoativos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Ingestão de Alimentos , Ativação Enzimática/efeitos dos fármacos , Fluorescência , Humanos , L-Lactato Desidrogenase/metabolismo , Lipopeptídeos/biossíntese , Lipopeptídeos/química , Óleos/química , Espectrometria de Massas por Ionização por Electrospray , Tensoativos/química , Tensoativos/metabolismo , Espectrometria de Massas em Tandem
20.
Braz J Microbiol ; 40(2): 373-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24031375

RESUMO

A lipopeptide biosurfactant produced by Bacillus natto TK-1 has a strong surface activity. The biosurfactant was found to be an anti-adhesive agent against several bacterial strains, and also showed a broad spectrum of antimicrobial activity. The biosurfactant induced a significant reduction in tumor cells viability in a dose-dependent manner.

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