Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Regul Toxicol Pharmacol ; 125: 105018, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34314750

RESUMO

Electronic Nicotine Delivery Systems (ENDS), i.e., electronic-cigarettes (e-cigs) and Tobacco Heating Products (THPs), are rapidly growing in popularity. Nonetheless, comprehensive quality and safety requirements for regulatory purposes are still under development. Cytotoxicity studies are important initial steps in appraising the potential ENDS toxicity. The aim of the present study was to screen different in vitro cytotoxicity methods for the assessment of ENDS toxicity. We evaluated NRU, MTT, Annexin V apoptosis (AN-V), High-Content Screening (HCS) assays and Real-Time Cell Analysis (RTCA), to compare two e-cigs and two THPs with the 1R6F reference tobacco cigarette. Human adenocarcinoma lung epithelial cells (H292) were exposed to tobacco smoke and ENDS vapor at air-liquid interface. All tests showed reduced cell viability following 1R6F smoke exposure and slight or no reduction with ENDS at 24 h. AN-V and RTCA exhibited a further significant reduction in cell viability following 1R6F exposure. AN-V allowed to discriminate viable cells from those in early/late apoptosis. RTCA and HCS being time-resolved analyses elucidate the kinetic dependency parameter for toxicity of smoke/vapor chemicals on cell viability. In conclusion, NRU assay may be considered a suitable test, especially when combined with a time-resolved analysis, for assessing the kinetic of cytotoxicity induced by these products.

3.
Antioxidants (Basel) ; 10(6)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067436

RESUMO

Glucose induces corneal epithelial dysfunctions characterized by delayed wound repair. Nuclear erythroid 2-related factor 2 (Nrf2) mediates cell protection mechanisms even through the Heme oxygenase-1 (HO-1) up-regulation. Here, we synthesized new HO-1 inducers by modifying dimethyl fumarate (DMF) and used docking studies to select VP13/126 as a promising compound with the best binding energy to Kelch-like ECH-associated protein 1 (keap1), which is the the regulator of Nrf2 nuclear translocation. We verified if VP13/126 protects SIRC cells from hyperglycemia compared to DMF. SIRC were cultured in normal (5 mM) or high glucose (25 mM, HG) in presence of DMF (1-25 µM) or VP13/126 (0.1-5 µM) with or without ERK1/2 inhibitor PD98059 (15 µM). VP13/126 was more effective than DMF in the prevention of HG-induced reduction of cell viability and proliferation. Reduction of wound closure induced by HG was similarly counteracted by 1 µM VP13/126 and 10 µM DMF. VP13/126 strongly increased phospho/total ERK1/2 and restored HO-1 protein in HG-treated SIRC; these effects are completely counteracted by PD98059. Moreover, high-content screening analysis showed a higher rate of Nrf2 nuclear translocation induced by VP13/126 than DMF in HG-stimulated SIRC. These data indicate that VP13/126 exerts remarkable pro-survival properties in HG-stimulated SIRC, promoting the Nrf2/HO-1 axis.

4.
Antibiotics (Basel) ; 10(4)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924336

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to public health, due to its large variety of pathogenetic mechanisms. Accordingly, the present study aimed to investigate the anti-MRSA activities of Krameria lappacea, a medicinal plant native to South America. Through Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass spectrometry, we analyzed the chemical composition of Krameria lappacea root extract (KLRE). The antibacterial activity of KLRE was determined by the broth microdilution method, also including the minimum biofilm inhibitory concentration and minimum biofilm eradication concentration. Besides, we evaluated the effect on adhesion and invasion of human lung carcinoma A549 cell line by MRSA strains. The obtained results revealed an interesting antimicrobial action of this extract, which efficiently inhibit the growth, biofilm formation, adhesion and invasion of MRSA strains. Furthermore, the chemical analysis revealed the presence in the extract of several flavonoid compounds and type-A and type-B proanthocyanidins, which are known for their anti-adhesive effects. Taken together, our findings showed an interesting antimicrobial activity of KLRE, giving an important contribution to the current knowledge on the biological activities of this plant.

5.
Front Pharmacol ; 12: 652102, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859566

RESUMO

Prevalence studies of current smoking, among hospitalized COVID-19 patients, demonstrated an unexpectedly low prevalence among patients with COVID-19. The aim of the present study was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 h from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1,012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.

6.
Endocrine ; 73(3): 712-718, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33751390

RESUMO

PURPOSE: Neuroactive steroids may have a role in regulating sexual function. This case-control study assessed whether dutasteride, a 5α-reductase inhibitor used for treatment of patients with benign prostate hyperplasia (BPH), impacts on the levels of neuroactive steroids, leading to erectile dysfunction (ED) and/or hypoactive sexual desire (HSD). METHODS: Forty patients with BPH and moderate-to-severe lower urinary tract symptoms (LUTS), pre-scheduled for prostate transurethral resection or open prostatectomy were enrolled. Twenty of these patients with prostate volume ≤40 mL were treated with α-blockers (Group A) and the remaining 20, with prostate volume >40 mL, with dutasteride plus α-blockers (Group B) for at least 6 months before surgery. Serum sex steroids and gonadotropin levels were measured the day before surgery, and the neuroactive steroid levels were assessed in the cerebrospinal fluid (CSF) collected during spinal anesthesia, at the day of surgery. RESULTS: Before surgery, the International Index of Erectile Function 5-item score was higher in Group A that Group B (18.8 ± 4.8 vs. 15.1 ± 5.4, p < 0.01). Group A showed lower total testosterone (TT) (4.5 vs.6.4 ng/ml, p < 0.01) and 17ß-estradiol (E2) (24.3 vs.30.7 pg/ml, p < 0.05) serum levels than Group B. CSF levels of TT (1446.6 vs. 19.9 pg/ml, p < 0.05) and dihydrotestosterone (7.9 vs. 1.4 pg/ml, p < 0.05) were higher and CSF E2 levels were lower (26.0 vs.36.0 pg/ml, p < 0.01) in Group A than Group B. CONCLUSIONS: A decrease of neuroactive steroids in the CSF of patients treated with dutasteride occurs. This may be one of the mechanisms by which dutasteride may cause ED and HSD.


Assuntos
Hiperplasia Prostática , Estudos de Casos e Controles , Di-Hidrotestosterona , Dutasterida/uso terapêutico , Humanos , Masculino , Hiperplasia Prostática/tratamento farmacológico , Esteroides
7.
Curr Pharm Biotechnol ; 22(7): 983-994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32881666

RESUMO

BACKGROUND: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. OBJECTIVE: The effect of combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. METHODS: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. RESULTS: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. Higher activity was correlated to the presence of flavors and nicotine. DISCUSSION: In most cases, the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to the presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. CONCLUSION: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.


Assuntos
Antibacterianos/farmacologia , Sistemas Eletrônicos de Liberação de Nicotina , Aromatizantes/farmacologia , Glicerol/farmacologia , Estudo de Prova de Conceito , Propilenoglicol/farmacologia , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/fisiologia , Testes de Sensibilidade Microbiana/métodos , Nicotina/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
8.
Int J Mol Sci ; 21(15)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32756477

RESUMO

Vascular pericytes are an important cellular component in the tumor microenvironment, however, their role in supporting cancer invasion is poorly understood. We hypothesized that PDGF-BB could be involved in the transition of human retinal pericytes (HRPC) in cancer-activated fibroblasts (CAF), induced by the 92.1 uveal melanoma (UM) cell line. In our model system, HRPC were conditioned by co-culturing with 92.1UM for 6 days (cHRPC), in the presence or absence of imatinib, to block PDGF receptor-ß (PDGFRß). The effects of the treatments were tested by wound healing assay, proliferation assay, RT-PCR, high-content screening, Western blot analysis, and invasion assay. Results showed profound changes in cHRPC shape, with increased proliferation and motility, reduction of NG2 and increase of TGF-ß1, α-SMA, vimentin, and FSP-1 protein levels, modulation of PDGF isoform mRNA levels, phospho-PDGFRß, and PDGFRß, as well as phospho-STAT3 increases. A reduction of IL-1ß and IFNγ and an increase in TNFα, IL10, and TGF-ß1, CXCL11, CCL18, and VEGF mRNA in cHRPC were found. Imatinib was effective in preventing all the 92.1UM-induced changes. Moreover, cHRPC elicited a significant increase of 92.1UM cell invasion and active MMP9 protein levels. Our data suggest that retinal microvascular pericytes could promote 92.1UM growth through the acquisition of the CAF phenotype.


Assuntos
Becaplermina/genética , Melanoma/metabolismo , Pericitos/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Neoplasias Uveais/metabolismo , Fibroblastos Associados a Câncer/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mesilato de Imatinib/farmacologia , Metaloproteinase 9 da Matriz/genética , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Proteínas de Neoplasias/genética , Pericitos/efeitos dos fármacos , Pericitos/patologia , Retina/metabolismo , Retina/patologia , Fator de Crescimento Transformador beta1/genética , Microambiente Tumoral/efeitos dos fármacos , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/genética , Neoplasias Uveais/patologia , Cicatrização
9.
Diabetes Metab Syndr Obes ; 13: 2433-2442, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753926

RESUMO

Background: Aerobic exercise can greatly assist in reducing collateral effects of metabolic syndrome (MetS). Moreover, aerobic exercise is associated with sympathetic activation and adaptive responses to sustain muscle engagement, changes in the release of Orexin A, a pleiotropic neuropeptide. Aim: The aim of this study was to analyze the beneficial effects of aerobic exercise without dietary changes, in a cohort of MetS subjects, focusing on the role of sympathetic and orexinergic activity. Several blood parameters linked to MetS ROS production, heart rate, galvanic skin response, d-ROM test, and Orexin A serum levels were evaluated in ten males with MetS (BMI 30-34.9) before and after a period of 6 months of aerobic exercise compared to ten healthy subjects. Methods: Ten male subjects (aged 54 ± 4.16) with MetS (MetS group) and ten healthy males (aged 49.7 ± 2.79, Healthy group) were told about the study protocol and possible risks, signed the informed consent, and voluntarily participated in the study. Several blood parameters were evaluated in the two tested groups and were re-evaluated in the MetS group after 6 months of training (MetS6M group). The training protocol consisted of more than 30 min/day of walking (average speed of 4.5 km/h) and 3 days/week of aerobic activities (jogging under heart rate control - 120-140 bpm for 45 min). Results: The results showed that exercise induced a significant increase in GSR and plasma Orexin A but no significant increase in d-ROM values. Significant decreases in the serum ALT enzyme, triglycerides, and total cholesterol were found, while the HDL levels were significantly higher. Finally, a significant reduction of BMI and resting HR were reported. Conclusion: The results of this study confirm that physical activity is associated with sympathetic activation, having a pivotal role against adverse effects linked to MetS. Moreover, this study demonstrates that, in patients with MetS, Orexin A is involved in hormonal adaptations to exercise.

10.
Liver Int ; 40(11): 2820-2827, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32666695

RESUMO

BACKGROUND AND AIMS: HCV eradication improves non-hepatic outcomes such as cardiovascular diseases, although without clearly defined mechanisms. In this study we aimed to assess whether improvement of carotid atherosclerosis may be linked to a reduction in systemic oxidative stress after viral clearance. METHODS: We studied a retrospective cohort of 105 patients (age 62.4 ± 11.2 years; 62 men) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow-up. Levels of 8-iso-prostaglandin F2α (F2 -isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) in oxidative stress markers (exposures) and change in carotid intima-media thickness (cIMT) (outcome) was examined using multiple linear regression. RESULTS: Subclinical atherosclerosis, defined as the presence of carotid plaque and/or cIMT ≥ 0.9, was present in 72% of the cohort. All patients achieved SVR that led to reduction in cIMT (0.92 ± 0.20 vs 0.83 ± 0.21 mm, P < .001). HCV eradication markedly decreased serum levels of F2 -isoprostanes (620.5 [143.2; 1904.1] vs 119.51 [63.2; 400.6] pg/mL, P < .0001), lipid hydroperoxides (13.8 [6.3; 20.7] vs 4.9 [2.3; 9.6] nmol/µl, P < .0001) and 8-hydroxy-2'-deoxyguanosine (558.9 [321.0; 6301.2] vs 294.51 [215.31; 408.95] pg/mL, P < .0001), whereas increased serum GPx activity (10.44 [4.6; 16.3] vs 13.75 [9.42; 20.63] nmol/min/mL, P = .001). By multiple linear regression analysis ΔcIMT was independently associated with ΔF2 -isoprostanes (ß: 1.746 [0.948; 2.543]; P < .0001) after adjustment for age, baseline F2 -isoprostanes and baseline IMT. CONCLUSIONS: Besides association of lipid peroxidation with severity of liver disease, the reduction in F2 -isoprostanes may be involved in the improvement of atherosclerosis after HCV eradication.


Assuntos
Hepacivirus , Hepatite C , Idoso , Antivirais/uso terapêutico , Espessura Intima-Media Carotídea , Hepatite C/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Retrospectivos
11.
Aging (Albany NY) ; 12(10): 9745-9760, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32401230

RESUMO

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. The most accurate prognostic factor of UM is classification by gene expression profiling. Currently, the role of epigenetics is much less defined compared to genetic mechanisms. We recently showed a strong prognostic role of the expression levels of histone variant macroH2A1 in UM patients. Here, we assessed the mechanistic effects of macroH2A1 on UM progression.UM cell lines were stably knocked down (KD) for macroH2A1, and proliferation and colony formation capacity were evaluated. Mitochondrial function was assayed through qPCR and HPLC analyses. Correlation between mitochondrial gene expression and cancer aggressiveness was studied using a bioinformatics approach.MacroH2A1 loss significantly attenuated UM cells proliferation and aggressiveness. Furthermore, genes involved in oxidative phosphorylation displayed a decreased expression in KD cells. Consistently, macroH2A1 loss resulted also in a significant decrease of mitochondrial transcription factor A (TFAM) expression, suggesting impaired mitochondrial replication. Bioinformatics analyses uncovered that the expression of genes involved in mitochondrial metabolism correlates with macroH2A1 and with cancer aggressiveness in UM patients. Altogether, our results suggest that macroH2A1 controls UM cells progression and it may represent a molecular target to develop new pharmacological strategies for UM treatment.


Assuntos
Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Histonas/deficiência , Melanócitos/metabolismo , Melanoma/genética , Neoplasias Uveais/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Humanos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/metabolismo
12.
J Oncol ; 2020: 2314693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32148493

RESUMO

Gliomas are the most common primary tumors of the central nervous system (CNS) in the adult. Previous data showed that estrogen affects cancer cells, but its effect is cell-type-dependent and controversial. The present study aimed to analyze the effects of estradiol (E2, 5 nM) in human glioblastoma multiforme U87-MG cells and how it may impact on cell proliferation and mitochondrial fitness. We monitored cell proliferation by xCELLigence technology and mitochondrial fitness by assessing the expression of genes involved in mitochondrial biogenesis (PGC1α, SIRT1, and TFAM), oxidative phosphorylation (ND4, Cytb, COX-II, COX IV, NDUFA6, and ATP synthase), and dynamics (OPA1, MNF2, MNF1, and FIS1). Finally, we evaluated Nrf2 nuclear translocation by immunocytochemical analysis. Our results showed that E2 resulted in a significant increase in cell proliferation, with a significant increase in the expression of genes involved in various mechanisms of mitochondrial fitness. Finally, E2 treatment resulted in a significant increase of Nrf2 nuclear translocation with a significant increase in the expression of one of its target genes (i.e., heme oxygenase-1). Our results suggest that E2 promotes proliferation in glioblastoma cells and regulate the expression of genes involved in mitochondrial fitness and chemoresistance pathway.

13.
Mol Neurobiol ; 57(5): 2436-2446, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32108290

RESUMO

In human glioma tumours, heme oxygenase-1 (HO-1) is overexpressed when compared with normal brain tissues and during oligodendroglioma progression. However, the molecular mechanisms mediated by HO-1 to promote glioblastoma remain unknown. We therefore aimed at investigating the effect of HO-1 expression and its selective enzymatic inhibition in two different cell lines (i.e. A172 and U87-MG). HO-1 was induced by hemin treatment (10 µM), and VP13/47 (100 µM) was used as a specific non-competitive inhibitor of HO-1 activity. Cell proliferation was measured by cell index measurement (xCelligence technology) and clonogenic assay, whereas cell migration was assessed by wound healing assay. Carbon monoxide-releasing molecules (CORMs) (i.e. CORM-3 and CORM-A1) were also used in a separate set of experiments to confirm the effect of HO-1 by-product in glioblastoma progression further. Our results were further validated using GSE4412 microarray dataset analysis and comparing biopsies overexpressing HO-1 with the rest of the cases. Our results showed that hemin was able to induce both HO-1 gene and protein expression in a cell-dependent manner being A172 more responsive to pharmacological upregulation of HO-1. Hemin, but not CORMs treatment, resulted in a significant increase of cell proliferation following 24 h of treatment as measured by increased cell index and colony formation capacity and such effect was abolished by VP13/47. Interestingly, both hemin and CORMs showed a significant effect on the wound healing assay also exhibiting cell specificity. Finally, our dataset analysis showed a positive correlation of HO-1 gene expression with ITGBI and ITGBII which are membrane receptors involved in cell adhesion, embryogenesis, tissue repair, immune response and metastatic diffusion of tumour cells. In conclusion, our data suggest that HO-1 and its by-product CO exhibit a cell-specific effect on various aspects of disease progression and are associated with a complex series of molecular mechanisms driving cell proliferation, survival and metastasis.


Assuntos
Neoplasias Encefálicas/patologia , Monóxido de Carbono/fisiologia , Glioblastoma/patologia , Heme Oxigenase-1/fisiologia , Proteínas de Neoplasias/fisiologia , Boranos/farmacologia , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Carbonatos/farmacologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quimiotaxia/efeitos dos fármacos , Conjuntos de Dados como Assunto , Progressão da Doença , Indução Enzimática/efeitos dos fármacos , Perfilação da Expressão Gênica , Ontologia Genética , Glioblastoma/enzimologia , Glioblastoma/genética , Heme Oxigenase-1/biossíntese , Heme Oxigenase-1/genética , Hemina/farmacologia , Humanos , Hidrocarbonetos Bromados/farmacologia , Imidazóis/farmacologia , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Compostos Organometálicos/farmacologia , Ensaio Tumoral de Célula-Tronco
14.
Aging Male ; 23(1): 14-22, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29950140

RESUMO

Impairment of antioxidant defense system and increase in metabolic rate and production of reactive oxygen species have been demonstrated in strenuous exercise. Both at rest and during contractile activity, skeletal muscle generates a very complex set of reactive nitrogen and oxygen species; the main generated are superoxide and nitric oxide. The nature of the contractile activity influences the pattern and the magnitude of this reactive oxygen and nitrogen species (ROS) generation. The intracellular pro-oxidant/antioxidant homeostasis undergoes alteration owing to strenuous exercise and the major identified sources of intracellular free radical generation during physical activity are the mitochondrial electron transport chain, polymorphoneutrophil, and xanthine oxidase. Reactive oxygen species increased tissue susceptibility to oxidative damage and pose a serious threat to the cellular antioxidant defense system. The possible dangerous consequences of the aging process and human wellness are emphasized in this review.


Assuntos
Envelhecimento/fisiologia , Exercício Físico/fisiologia , Músculo Esquelético/metabolismo , Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Humanos , Masculino , Contração Muscular/fisiologia , Estresse Oxidativo/fisiologia
15.
Cancers (Basel) ; 11(4)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974805

RESUMO

Epidemiological studies suggest that chronic alcohol consumption is a lifestyle risk factor strongly associated with colorectal cancer development and progression. The aim of the present study was to examine the effect of ethanol (EtOH) on survival and progression of three different colon cancer cell lines (HCT116, HT29, and Caco-2). Our data showed that EtOH induces oxidative and endoplasmic reticulum (ER) stress, as demonstrated by reactive oxygen species (ROS) and ER stress markers Grp78, ATF6, PERK and, CHOP increase. Moreover, EtOH triggers an autophagic response which is accompanied by the upregulation of beclin, LC3-II, ATG7, and p62 proteins. The addition of the antioxidant N-acetylcysteine significantly prevents autophagy, suggesting that autophagy is triggered by oxidative stress as a prosurvival response. EtOH treatment also upregulates the antioxidant enzymes SOD, catalase, and heme oxygenase (HO-1) and promotes the nuclear translocation of both Nrf2 and HO-1. Interestingly, EtOH also upregulates the levels of matrix metalloproteases (MMP2 and MMP9) and VEGF. Nrf2 silencing or preventing HO-1 nuclear translocation by the protease inhibitor E64d abrogates the EtOH-induced increase in the antioxidant enzyme levels as well as the migration markers. Taken together, our results suggest that EtOH mediates both the activation of Nrf2 and HO-1 to sustain colon cancer cell survival, thus leading to the acquisition of a more aggressive phenotype.

16.
Int J Mol Sci ; 20(3)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717203

RESUMO

Ozone therapy has been widely used in everyday clinical practice over the last few years, leading to significant clinical results in the treatment of herniated discs and pain management. Nevertheless, further studies have demonstrated its potential efficacy and safety under other clinical and experimental conditions. However, some of these studies showed controversial results regarding the safety and efficacy of ozone therapy, thus mining its potential use in an everyday clinical practice. To this regard, it should be considered that extensive literature review reported the use of ozone in a significant different dose range and with different delivery systems. The aim of the present review is to describe the various pharmacological effects of ozone in different organs and clinical conditions and to provide possible biochemical and molecular insights for ozone biological properties, thus providing a possible explanation for various controversial clinical outcomes described in the scientific literature.


Assuntos
Doenças Cardiovasculares/terapia , Degeneração do Disco Intervertebral/terapia , Deslocamento do Disco Intervertebral/terapia , Ozônio/administração & dosagem , Dor/prevenção & controle , Substâncias Protetoras/administração & dosagem , Dermatopatias/terapia , Doença Aguda , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Quimiotaxia/efeitos dos fármacos , Quimiotaxia/imunologia , Doença Crônica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/imunologia , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/imunologia , Degeneração do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/imunologia , Deslocamento do Disco Intervertebral/patologia , Estresse Oxidativo , Ozônio/efeitos adversos , Dor/genética , Dor/imunologia , Dor/patologia , Manejo da Dor/métodos , Substâncias Protetoras/efeitos adversos , Dermatopatias/genética , Dermatopatias/imunologia , Dermatopatias/patologia
17.
Mol Neurobiol ; 56(2): 1451-1460, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29948946

RESUMO

Neuroblastoma (NB) is an embryonic malignancy affecting the physiological development of adrenal medulla and paravertebral sympathetic ganglia in early infancy. Proteasome inhibitors (PIs) (i.e., carfilzomib (CFZ)) may represent a possible pharmacological treatment for solid tumors including NB. In the present study, we tested the effect of a novel non-competitive inhibitor of heme oxygenase-1 (HO-1), LS1/71, as a possible adjuvant therapy for the efficacy of CFZ in neuroblastoma cells. Our results showed that CFZ increased both HO-1 gene expression (about 18-fold) and HO activity (about 8-fold), following activation of the ER stress pathway. The involvement of HO-1 in CFZ-mediated cytotoxicity was further confirmed by the protective effect of pharmacological induction of HO-1, significantly attenuating cytotoxicity. In addition, HO-1 selective inhibition by a specific siRNA increased the cytotoxic effect following CFZ treatment in NB whereas SnMP, a competitive pharmacological inhibitor of HO, showed no changes in cytotoxicity. Our data suggest that treatment with CFZ produces ER stress in NB without activation of CHOP-mediated apoptosis, whereas co-treatment with CFZ and LS1/71 led to apoptosis activation and CHOP expression induction. In conclusion, our study showed that treatment with the non-competitive inhibitor of HO-1, LS1 / 71, increased cytotoxicity mediated by CFZ, triggering apoptosis following ER stress activation. These results suggest that PIs may represent a possible pharmacological treatment for solid tumors and that HO-1 inhibition may represent a possible strategy to overcome chemoresistance and increase the efficacy of chemotherapic regimens.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Heme Oxigenase (Desciclizante)/efeitos dos fármacos , Oligopeptídeos/farmacologia , Inibidores de Proteassoma/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia
18.
Mar Drugs ; 15(11)2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29104260

RESUMO

Resistance to chemotherapy occurs in various diseases (i.e., cancer and infection), and for this reason, both are very difficult to treat. Therefore, novel antimicrobial and chemotherapic drugs are needed for effective antibiotic therapy. The aim of the present study was to assess the antimicrobial and anti-proliferative effects of skin mucus derived from Dasyatis pastinaca (Linnaeus, 1758). Our results showed that skin mucus exhibited a significant and specific antibacterial activity against Gram-negative bacteria but not against Gram-positive bacteria. Furthermore, we also observed a significant antifungal activity against some strains of Candida spp. Concerning anti-proliferative activity, we showed that fish mucus was specifically toxic for acute leukemia cells (HL60) with an inhibition of proliferation in a dose dependent manner (about 52% at 1000 µg/mL of fish skin mucous, FSM). Moreover, we did not observe effects in healthy cells, in neuroblastoma cells (SH-SY5Y), and multiple myeloma cell lines (MM1, U266). Finally, it exhibited strong expression and activity of chitinase which may be responsible, at least in part, for the aforementioned results.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Organismos Aquáticos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Muco/química , Rajidae , Animais , Antibacterianos/química , Antineoplásicos/química , Relação Dose-Resposta a Droga , Células HL-60/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana
19.
Front Oncol ; 7: 243, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29075616

RESUMO

Prostate cancer (PCa) has become the most frequent type of cancer in men. Recent data suggest that diabetic patients taking metformin have a lower incidence of certain cancer, including PCa. Metformin is the most common drug used in type II diabetes mellitus; its use has been shown to lower the incidence of several cancers, although there are ambiguous data about the anticancer activity of metformin. A large number of studies examined the potential antineoplastic mechanism of metformin although it is not still completely understood. This review summarizes the literature concerning the effects of metformin on PCa cells, highlighting its numerous mechanisms of action through which it can act. We analyze the possible causes of the discordances regarding the impact of metformin on risk of PCa; we discuss the latest findings in this field, suggesting that metformin may have a future role in the management of PCa both as monotherapy and in combination with other drugs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...