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1.
Am J Hypertens ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202627

RESUMO

OBJECTIVES: We aimed to assess the hypertension (HTN) awareness and associated factors in France. METHODS: We conducted a cross-sectional analysis using data from the CONSTANCES population-based cohort involving 87,808 volunteer participants included between 2012 and 2018. HTN was defined as average blood pressure (BP) over 140/90 or use of BP medication, awareness as self-reported HTN. Multivariable logistic regression models were used to identify the associated factors. RESULTS: Overall, 27,160 hypertensive participants (men = 16,569) above 18 years old were analyzed. Hypertension awareness rate was 37.5%. In the multivariable regression model, awareness was predicted by female gender, age, prior cardiovascular disease (CVD), presence of diabetes mellitus (DM), presence of chronic kidney disease (CKD), level of education, and obesity or overweight. Older participants (P < 0.001), females (P < 0.001), participants with comorbidities (P < 0.001), were more likely to be aware when compared with younger participants, males and participants without comorbidities, respectively. The unawareness among participants without cardiometabolic factors (CMF, i.e., CVD, DM, CKD) was higher than participants with CMF (67% vs. 41%, respectively, P < 0.001). Moreover, some differences appeared in both genders in the association between awareness of HTN and health and lifestyle factors. CONCLUSION: Our findings show that HTN awareness is low. Particular attention should be given to young men without comorbidities as these characteristics were predictors of poor awareness. Immediate action is required to improve HTN awareness in France.

2.
Aging (Albany NY) ; 12(3): 3095-3113, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32035419

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease, where the etiology remains unclear. AD is characterized by amyloid-(Aß) protein aggregation and neurofibrillary plaques deposits. Oxidative stress and chronic inflammation have been suggested as causes of AD. Glutamatergic pathway dysregulation is also mainly associated with AD process. In AD, the canonical WNT/ß-catenin pathway is downregulated. Downregulation of WNT/ß-catenin, by activation of GSK-3ß-induced Aß, and inactivation of PI3K/Akt pathway involve oxidative stress in AD. The downregulation of the WNT/ß-catenin pathway decreases the activity of EAAT2, the glutamate receptors, and leads to neuronal death. In AD, oxidative stress, neuroinflammation and glutamatergic pathway operate in a vicious circle driven by the dysregulation of the WNT/ß-catenin pathway. Riluzole is a glutamate modulator and used as treatment in amyotrophic lateral sclerosis. Recent findings have highlighted its use in AD and its potential increase power on the WNT pathway. Nevertheless, the mechanism by which Riluzole can operate in AD remains unclear and should be better determine. The focus of our review is to highlight the potential action of Riluzole in AD by targeting the canonical WNT/ß-catenin pathway to modulate glutamatergic pathway, oxidative stress and neuroinflammation.

3.
Int J Mol Sci ; 21(3)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32012797

RESUMO

Age-related macular degeneration (AMD) is considered as the main worldwide cause of blindness in elderly adults. Exudative AMD type represents 10 to 15% of macular degeneration cases, but is the main cause of vision loss and blindness. Circadian rhythm changes are associated with aging and could further accelerate it. However, the link between circadian rhythms and exudative AMD is not fully understood. Some evidence suggests that dysregulation of circadian functions could be manifestations of diseases or could be risk factors for the development of disease in elderly adults. Biological rhythms are complex systems interacting with the environment and control several physiological pathways. Recent findings have shown that the dysregulation of circadian rhythms is correlated with exudative AMD. One of the main pathways involved in exudative AMD is the canonical WNT/ß-catenin pathway. Circadian clocks have a main role in some tissues by driving the circadian expression of genes involved in physiological and metabolic functions. In exudative AMD, the increase of the canonical WNT/ß-catenin pathway is enhanced by the dysregulation of circadian rhythms. Exudative AMD progression is associated with major metabolic reprogramming, initiated by aberrant WNT/ß-catenin pathway, of aerobic glycolysis. This review focuses on the interest of circadian rhythm dysregulation in exudative AMD through the aberrant upregulation of the canonical WNT/ß-catenin pathway.

4.
Sci Rep ; 10(1): 1925, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024888

RESUMO

From an epidemiological standpoint, quantifying the individual and the combined effect of lifestyle factors on uncontrolled blood pressure (BP) deserves further evaluation. We aimed to examine the individual and combined associations between unhealthy behaviors and uncontrolled hypertension among treated hypertensive adults. Cross-sectional analysis was conducted using data from CONSTANCES, an ongoing French population-based cohort study. Uncontrolled BP was defined as mean systolic BP ≥140 mmHg and/or mean diastolic BP ≥90 mmHg. Unhealthy behaviors were considered as heavy alcohol consumption, low or medium adherence to dietary recommendations, sedentary physical activity level, and overweight. A total of 10,710 hypertensive treated volunteer participants were included and 56.1% had uncontrolled hypertension; of them, 2.0%, 24.5%, 54.0% and 19.5% exhibited 0, 1, 2 or ≥3 unhealthy behaviors respectively. In men, there was an increased odds of uncontrolled hypertension with heavy alcohol drinking compared to light-or-never (adjusted odds ratio 1.34, 95% CI 1.10-1.63), with low as well as with medium adherence to dietary recommendations compared to high (p < 0.05 for both), and with overweight or obesity compared to a normal body mass index (p ≤ 0.001 for both). In addition, men reporting a combination of ≥3 unhealthy behaviors compared to none, had an increased odds of hypertension of 1.67 (95% CI 1.09-2.53). Unhealthy behaviors described as, heavy alcohol consumption, non-adherence to dietary recommendations and overweight are associated with uncontrolled hypertension, at the individual and combined level, and particularly in men. Improvement of modifiable lifestyle factors could offer considerable benefits in the management of hypertension.

5.
Cells ; 9(2)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012898

RESUMO

Parkinson's disease (PD) is one of the main neurodegenerative disease characterized by a progressive degeneration of neurons constituted by dopamine in the substantia nigra pars compacta. The etiologies of PD remain unclear. Aging is the main risk factor for PD. Aging could dysregulate molecular pathways controlling cell homeostatic mechanisms. PD cells are the sites of several metabolic abnormalities including neuroinflammation and oxidative stress. Metabolic structures are driven by circadian rhythms. Biologic rhythms are complex systems interacting with the environment and controlling several physiological pathways. Recent findings have shown that the dysregulation of the circadian rhythms is correlated with PD and its metabolic dysregulations. This review is focused on the key role of circadian rhythms and their impact on neuroinflammation and oxidative stress in Parkinson's disease.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32092238

RESUMO

The purposes of this study were to describe the hypertensive population and therapeutic management of hypertension in adults between 18 and 74 years of age in France in 2015. Esteban survey is a cross-sectional survey with a clinical examination conducted in a representative sample of French adults aged 18-74 years between 2014 and 2016. Esteban was entirely public-funded. Blood pressure (BP) was measured during clinical examination with a standardized protocol, and pharmacological treatment was collected through the exhaustive Système National des Données de Santé (SNDS) database. Hypertension was defined by systolic BP (SBP)> 140 mm Hg, diastolic BP (DBP)> 90 mm Hg or treatment with BP-lowering drugs. The therapeutic control of treated hypertensive patients was defined by SBP < 140 mm Hg and DBP < 90 mm Hg. Adherence to drug treatment was defined as more than 80% of days covered by BP-lowering drug per year. The prevalence of hypertension was 31.3%. 74.7% of aware hypertensive participants taking an antihypertensive drug, and 57.7% of them were treated with a single antihypertensive pharmacological class. Overall, among hypertensives, 24.3% had a satisfactory BP control. Only 49.7% of treated hypertensives participants were controlled, and 33.6% of them were adherent to their drug treatment. The prevalence of hypertension in France remains high, with only 74.7% of the aware hypertensive participants receiving pharmacological therapy and only 48.9% of aware hypertensives with a BP at goal. More effective measures are needed to improve clinical management of hypertension in France.

7.
Curr Hypertens Rep ; 22(1): 5, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925555

RESUMO

PURPOSE OF REVIEW: Aortic stiffness (AS) is widely associated with hypertension and considered as a major predictor of coronary heart disease (CHD). AS is measured using carotid-femoral pulse wave velocity (PWV), particularly when this parameter is associated with an index involving age, gender, heart rate, and mean blood pressure. The present review focuses on the interest of measurement of PWV and the calculation of individual PWV index for the prediction of CHD, in addition with the use of new statistical nonlinear models enabling results with very high levels of accuracy. RECENT FINDINGS: PWV index may so constitute a substantial marker of large arteries prediction and damage in CHD and may be also used in cerebrovascular and renal circulations models. PWV index determinations are particularly relevant to consider in angiographic CHD decisions and in the presence of vulnerable plaques with high cardiovascular risk. Due to the variability in symptoms and clinical characteristics of patients, together with some imperfections in results, there is no very simple adequate diagnosis approach enabling to improve the so defined CHD prediction in usual clinical practice. In recent works in relation to "artificial intelligence" and involving "decision tree" models and "artificial neural networks," it has been possible to determine consistent pathways introducing predictive medicine and enabling to obtain efficient algorithm classification models of coronary prediction.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31950414

RESUMO

Cadmium is inconsistently associated with blood pressure (BP) and hypertension. Our study focuses to understand the association between urinary cadmium levels, blood pressure, and hypertension in a French representative sample. Our study included 2015 subjects from the ESTEBAN survey (2014-2015) with measured urinary cadmium. Associations between natural logarithm-transformed cadmium levels and BP (systolic (SBP) and diastolic blood pressure (DBP)) were performed by adjusted linear regression models. Associations between cadmium and hypertension were performed by adjusted logistic regression models. Models were stratified by gender, smoking habits, body mass index (BMI), and kidney function categories. Men present higher SBP (131.7 vs. 121.5 mmHg, p < 0.0001) and DBP (78.9 vs. 74.7 mmHg, p < 0.0001) in comparison to women. Creatinine-adjusted urinary cadmium levels (0.48 vs. 0.39 µg/L, p < 0.0001) were higher in hypertensive subjects. Nevertheless, no difference was observed after adjustment for age, gender, and smoking habits. No correlation between urinary cadmium, BP, and hypertension was observed in overall population. Stratified models showed inverse correlations between urinary cadmium and hypertension among obese (OR = 0.39, 95% CI [0.21-0.57], p = 0.0009), chronic kidney function (OR = 0.68 95%CI [0.75-0.97], p = 0.003), and current smokers (OR = 0.78, 95% CI [0.64-0.92], p = 0.04). A correlation between urinary cadmium levels, BP, and hypertension is observed in subpopulations. Nevertheless, directions and significance of these associations differs by gender, BMI, smoking, and kidney function categories.

9.
J Hypertens ; 38(2): 249-256, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31460994

RESUMO

BACKGROUND: Increased aortic stiffness could be one of the mechanisms by which obesity increases cardiovascular risk independently of traditional risk factors. Studies have suggested that anthropometric indices may be predictors of cardiovascular risk but few studies have investigated their relations with aortic stiffness in high cardiovascular risk population. We investigated the strength of correlation between different anthropometric indices with aortic stiffness in hypertensive and diabetic patients. METHODS: A cross-sectional study was performed in 474 hypertensive patients. Anthropometric indices were calculated: BMI, waist circumference, waist-hip ratio, and waist-height ratio (WHtR). Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV). Correlations between indices and PWV were investigated by linear regression analyses and hierarchical analyses after adjusting for cardiovascular risk factors. RESULTS: Regional anthropometric indices were more strongly correlated with PWV than BMI in both sexes. In linear regression analyses, WHtR presented the highest correlation with PWV than other indices in our study population. In adjusted hierarchical regression used, WHtR had the highest additive value on top of BMI while there no additive value of BMI on top of WHtR. These differences remained after adjustment on cardiovascular events. In men WHtR was more closely correlated with PWV than others. In women, waist-hip ratio and WHtR were equally correlated with PWV compared with BMI. CONCLUSION: Regional anthropometric indices are more closely correlated with PWV than BMI in hypertensive patients. WHtR presents the highest correlation with PWV beyond BMI. REGISTRATION: The study was registered in the French National Agency for Medicines and Health Products Safety (No. 2013-A00227-38) and was approved by the Advisory Committee for Protection of Persons in Biomedical Research.

11.
Front Oncol ; 9: 1248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803621

RESUMO

Canonical WNT/ß-catenin signaling is involved in most of the mechanisms that lead to the formation and development of cancer cells. It plays a central role in three cyclic processes, which are the cell division cycle, the immune cycle, and circadian rhythms. When the canonical WNT pathway is upregulated as in cancers, the increase in ß-catenin in the nucleus leads to activation of the expression of numerous genes, in particular CYCLIN D1 and cMYC, where the former influences the G1 phase of the cell division cycle, and the latter, the S phase. Every stage of the immune cycle is disrupted by the canonical WNT signaling. In numerous cancers, the dysfunction of the canonical WNT pathway is accompanied by alterations of the circadian genes (CLOCK, BMAL1, PER). Induction of these cyclic phenomena leads to the genesis of thermodynamic mechanisms that operate far from equilibrium, and that have been called "dissipative structures." Moreover, upregulation of the canonical WNT/ß-catenin signaling is important in the myofibroblasts of the cancer stroma. Their differentiation is controlled by the canonical WNT /TGF-ß1 signaling. Myofibroblasts present ultraslow contractile properties due to the presence of the non-muscle myosin IIA. Myofibroblats also play a role in the inflammatory processes, often found in cancers and fibrosis processes. Finally, upregulated canonical WNT deviates mitochondrial oxidative phosphorylation toward the Warburg glycolysis metabolism, which is characteristic of cancers. Among all these cancer-generating mechanisms, the upregulated canonical WNT pathway would appear to offer the best hope as a therapeutic target, particularly in the field of immunotherapy.

12.
Cell Biosci ; 9: 98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827764

RESUMO

Myofibroblasts are non-muscle contractile cells that play a key physiologically role in organs such as the stem villi of the human placenta during physiological pregnancy. They are able to contract and relax in response to changes in the volume of the intervillous chamber. Myofibroblasts have also been observed in several diseases and are involved in wound healing and the fibrotic processes affecting several organs, such as the liver, lungs, kidneys and heart. During the fibrotic process, tissue retraction rather than contraction is correlated with collagen synthesis in the extracellular matrix, leading to irreversible fibrosis and, finally, apoptosis of myofibroblasts. The molecular motor of myofibroblasts is the non-muscle type IIA and B myosin (NMMIIA and NMMIIB). Fibroblast differentiation into myofibroblasts is largely governed by the transforming growth factor-ß1 (TGF-ß1). This system controls the canonical WNT/ß-catenin pathway in a positive manner, and PPARγ in a negative manner. The WNT/ß-catenin pathway promotes fibrosis, while PPARγ prevents it. This review focuses on the contractile properties of myofibroblasts and the conductor, TGF-ß1, which together control the opposing interplay between PPARγ and the canonical WNT/ß-catenin pathway.

13.
J Hypertens ; 37(12): 2499-2500, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31688294
15.
PLoS One ; 14(10): e0222683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31574082

RESUMO

Mesenchymal stem cells (MSCs) were obtained from human bone marrow and amplified in cultures supplemented with human platelet lysate in order to generate myofibroblasts. When MSCs were seeded in solid collagen scaffolds, they differentiated into myofibroblasts that were observed to strongly bind to the substrate, forming a 3D cell scaffold network that developed tension and shortening after KCl stimulation. Moreover, MSC-laden scaffolds recapitulated the Frank-Starling mechanism so that active tension increased in response to increases in the initial length of the contractile system. This constituted a bioengineering tissue that exhibited the contractile properties observed in both striated and smooth muscles. By using the A. F. Huxley formalism, we determined the myosin crossbridge (CB) kinetics of attachment (f1) and detachment (g1 and g2), maximum myosin ATPase activity, molar myosin concentration, unitary CB force and maximum CB efficiency. CB kinetics were dramatically slow, characterizing the non-muscle myosin type IIA (NMMIIA) present in myofibroblasts. When MSCs were seeded in solid collagen scaffolds functionalized with Arg-Gly-Asp (RGD), contractility increased and CB kinetics were modified, whereas the unitary NMMIIA-CB force and maximum CB efficiency did not change. In conclusion, we provided a non-muscle bioengineering tissue whose molecular mechanical characteristics of NMMIIA were very close to those of a non-muscle contractile tissue such as the human placenta.

16.
J Hypertens ; 37(11): 2180-2189, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31584898

RESUMO

OBJECTIVES: We aimed to evaluate the individual and combined association between unhealthy behavior and hypertension (HTN). METHODS: We conducted cross-sectional analysis using data from the population-based cohort study CONSTANCES. Blood pressure measurements were taken based on standardized operational procedures. Dietary adherence was done following the dietary approach to stop HTN diet. We considered heavy alcohol drinking, sedentary-level physical activity, low/medium dietary adherence and overweight/obesity as unhealthy behaviors. Participants' characteristics were compared according to the number of unhealthy behaviors and the association between HTN and unhealthy behaviors was estimated using logistic regression. RESULTS: A total of 86 448 volunteer participants were included and the prevalence of HTN was of 31.1%. Of those with HTN, 8.2, 33.0, 44.3 and 14.5% exhibited 0, 1, 2 or at least 3 unhealthy behaviors, respectively. In both sexes, the prevalence of HTN increased with low/medium dietary adherence compared with high (P < 0.01), in overweight/obese compared with normal BMI (P < 0.001), with heavy alcohol consumption compared with moderate or never (P < 0.05) and with sedentary physical activity level compared to high in women only (P = 0.049). Combination of several unhealthy behaviors was associated with increased odds of HTN (P trend <0.001); men reporting 2 or at least 3 unhealthy behaviors had an adjusted odds ratio of HTN of 1.77 and 2.29, respectively, while women had an adjusted odds ratio of 1.71 and 2.14, respectively. CONCLUSION: Individual and combined unhealthy lifestyle factors were strongly associated with HTN in this large population-based study.

17.
J Clin Hypertens (Greenwich) ; 21(10): 1484-1492, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31479194

RESUMO

Aortic stiffness is a marker of vascular aging and may reflect occurrence of cardiovascular (CV) diseases. Aortic pulse wave velocity (PWV), a marker of aortic stiffness, can be measured by applanation tonometry. A nomogram of aortic stiffness was evaluated by the calculation of PWV index. Theoretical PWV can be calculated according to age, gender, mean blood pressure, and heart rate, allowing to form an individual PWV index [(measured PWV - theoretical PWV)/theoretical PWV]. The purpose of the present cross-sectional study was to investigate the determinants of the PWV index, by applying a decision tree. A cross-sectional study was conducted from 2012 to 2017, and 597 individuals were included. A training decision tree was constructed based on seventy percent of these subjects (N = 428). The remaining 30% (N = 169) were used as the testing dataset to evaluate the performance of the decision trees. The input variables for the models were clinical and biochemical parameters. The different input variables remained in the model were diabetes, tobacco status, carotid plaque, albuminuria, C-reactive protein, total cholesterol, BMI, and previous CV diseases. For the validation decision model, the sensitivity, specificity, and accuracy values for identifying the related risk factors of PWV index were 70%, 78%, and 0.73. Since determinants of PWV index were all well-accepted CV risk factors, a nomogram of aortic stiffness could be considered as an integrator of CV risk factors on their duration of exposure and could be utilized to develop future programs for CV risk assessment and reduction strategies.

18.
J Exp Clin Cancer Res ; 38(1): 323, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331376

RESUMO

Numerous studies have presented that curcumin could have a positive effect in the prevention of cancer and then in tumor therapy. Several hypotheses have highlighted that curcumin could decreases tumor growth and invasion by acting on both chronic inflammation and oxidative stress. This review focuses on the interest of use curcumin in cancer therapy by acting on the WNT/ß-catenin pathway to repress chronic inflammation and oxidative stress. In the cancer process, one of the major signaling pathways involved is the WNT/ß-catenin pathway, which appears to be upregulated. Curcumin administration participates to the downregulation of the WNT/ß-catenin pathway and thus, through this action, in tumor growth control. Curcumin act as PPARγ agonists. The WNT/ß-catenin pathway and PPARγ act in an opposed manner. Chronic inflammation, oxidative stress and circadian clock disruption are common and co-substantial pathological processes accompanying and promoting cancers. Circadian clock disruption related to the upregulation of the WNT/ß-catenin pathway is involved in cancers. By stimulating PPARγ expression, curcumin can control circadian clocks through the regulation of many key circadian genes. The administration of curcumin in cancer treatment would thus appear to be an interesting therapeutic strategy, which acts through their role in regulating WNT/ß-catenin pathway and PPARγ activity levels.


Assuntos
Curcumina/uso terapêutico , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , PPAR gama/genética , Proliferação de Células/efeitos dos fármacos , Relógios Circadianos/efeitos dos fármacos , Relógios Circadianos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/antagonistas & inibidores , Via de Sinalização Wnt/efeitos dos fármacos
19.
Blood Press ; 28(6): 375-384, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31293183

RESUMO

Background: Non-invasive tests leading to elective coronary angiography (CAG) have low diagnostic yield for obstructive coronary heart disease (CHD). Aortic stiffness, an independent predictor of CHD events can be easily measured by pulse wave velocity (PWV). We aimed at retrospectively evaluating the diagnostic accuracy PWV index to detect CHD in consecutive patients with suspected CHD that underwent CAG.Method: In population of 86 healthy patients with available PWV data, a theoretical PWV was derived. In different population of 62 individuals who underwent CAG for suspected CHD, PWV index was calculated as index [(measured PWV - theoretical PWV)/theoretical PWV]. Logistic regression and comparisons between ROC curves were used to add value of CAG indication performance of PWV index.Results: Out of 62, seventeen patients presented obstructive CHD and 22 patients had non-obstructive CHD. PWV index and severity of CHD were positively correlated (p < 0.0001). After applying several models that included classical CHD predictor, the higher performance to detect abnormal CAG was obtained with the combined classifier PWV index/carotid plaque with 87% sensitivity, 93% specificity, 0.92 accuracy and 0.31 threshold. To detect obstructive CAG, individual classifier PWV index presents 94% sensitivity, 91% specificity, 0.95 accuracy and 0.46 threshold.Conclusion: PWV index is individualized approach that optimizes CHD diagnostic strategies and thus might be clinically useful for reducing the rate of unnecessary invasive CAG.

20.
Cells ; 8(7)2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311204

RESUMO

Chronic inflammation and oxidative stress are common and co-substantial pathological processes accompanying and contributing to cancers. Numerous epidemiological studies have indicated that non-steroidal anti-inflammatory drugs (NSAIDs) could have a positive effect on both the prevention of cancer and tumor therapy. Numerous hypotheses have postulated that NSAIDs could slow tumor growth by acting on both chronic inflammation and oxidative stress. This review takes a closer look at these hypotheses. In the cancer process, one of the major signaling pathways involved is the WNT/ß-catenin pathway, which appears to be upregulated. This pathway is closely associated with both chronic inflammation and oxidative stress in cancers. The administration of NSAIDs has been observed to help in the downregulation of the WNT/ß-catenin pathway and thus in the control of tumor growth. NSAIDs act as PPARγ agonists. The WNT/ß-catenin pathway and PPARγ act in opposing manners. PPARγ agonists can promote cell cycle arrest, cell differentiation, and apoptosis, and can reduce inflammation, oxidative stress, proliferation, invasion, and cell migration. In parallel, the dysregulation of circadian rhythms (CRs) contributes to cancer development through the upregulation of the canonical WNT/ß-catenin pathway. By stimulating PPARγ expression, NSAIDs can control CRs through the regulation of many key circadian genes. The administration of NSAIDs in cancer treatment would thus appear to be an interesting therapeutic strategy, which acts through their role in regulating WNT/ß-catenin pathway and PPARγ activity levels.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Relógios Circadianos/efeitos dos fármacos , Humanos , Neoplasias/metabolismo , PPAR gama/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
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