RESUMEN
BACKGROUND/AIM: The aim of this study was to analyze rs2234693 and rs9340799 polymorphisms of the ESR1 gene in the context of breast cancer risk in Polish patients. MATERIALS AND METHODS: The study involved a group of 117 patients with breast cancer and 106 controls. The analyses were carried out using the polymerase chain reaction - restriction fragments length polymorphism technique. RESULTS: The presence of the CC genotype in rs2234693 more than doubled the risk of breast cancer (p=0.04), whereas the presence of the TT genotype in rs2234693 significantly reduced the risk of developing this type of cancer (p=0.0002). The presence of the GG genotype in rs9340799 more than doubled the risk of breast cancer (p=0.04), which was confirmed by the analysis of the recessive model (p=0.04). CONCLUSION: The polymorphisms rs2234693 and rs9340799 of the ESR1 gene may be associated with the risk of breast cancer among Polish women.
Asunto(s)
Neoplasias de la Mama , Receptor alfa de Estrógeno , Predisposición Genética a la Enfermedad , Genotipo , Polimorfismo de Nucleótido Simple , Humanos , Receptor alfa de Estrógeno/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Femenino , Persona de Mediana Edad , Adulto , Polonia/epidemiología , Estudios de Casos y Controles , Factores de Riesgo , Alelos , Frecuencia de los Genes , Anciano , Estudios de Asociación GenéticaRESUMEN
The coordinated action of VEGF, IGF1/2 and H19 factors influences the development of endometriosis. The aim of this study was to analyze the expression level of these genes in patients with endometriosis. The study group consisted of 100 patients who were diagnosed with endometriosis on laparoscopic and pathological examination. The control group consisted of 100 patients who were found to be free of endometriosis during the surgical procedure and whose eutopic endometrium wasnormal on histopathological examination. These patients were operated on for uterine fibroids. Gene expression was determined by RT-PCR. The expression of the VEGF gene was significantly higher in the samples classified as clinical stage 1-2 compared to the control material (p < 0.05). There was also a statistically significant difference between the samples studied at clinical stages 1-2 and 3-4 (p < 0.01). The expression of the VEGF gene in the group classified as 1-2 was significantly higher. IGF1 gene expression was significantly lower both in the group of samples classified as clinical stages 1-2 and 3-4 compared to the control group (p < 0.05 in both cases). The expression of the H19 gene was significantly lower in the group of samples classified as clinical stage 3-4 compared to the control group (p < 0.01). The reported studies suggest significant roles of VEGF, IGF and H19 expression in the pathogenesis of endometriosis.
Asunto(s)
Endometriosis , Factor II del Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina , ARN Largo no Codificante , Factor A de Crecimiento Endotelial Vascular , Humanos , Femenino , Endometriosis/genética , Endometriosis/metabolismo , Endometriosis/patología , ARN Largo no Codificante/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Adulto , Polonia , Persona de Mediana Edad , Regulación de la Expresión Génica , Estudios de Casos y ControlesRESUMEN
This review contains the results of Polish (Central Europe) ethnomedical studies that describe the treatment of urinary tract diseases with wild and cultivated plants. The study includes only the plants that are used to treat the urinary tract, excluding prostate diseases. A review of the literature was carried out to verify the pharmacological use of the plants mentioned in the interviews. Based on this, the study reviews the pharmacological activities of all the recorded species and indicates their most important chemical compounds. Fifty-three species (belonging to 30 families) were selected for the study. The Compositae (eight species), Rosaceae (six species), and Apiaceae (six species) are the most common families used in the treatment of urinary diseases in Polish folk medicine. Both in vitro and in vivo studies have confirmed that many of these plant species have beneficial properties, such as diuretic, antihyperuricemic, antimicrobial, and anti-inflammatory activity, or the prevention of urinary stone formation. These effects are exerted through different mechanisms, for example, through the activation of bradykinin B2 receptors, inhibition of xanthine oxidase, or inhibition of Na+-K+ pump. Many plants used in folk medicine are rich in phytochemicals with proven effectiveness against urinary tract diseases, such as rutin, arbutin, or triterpene saponins.
RESUMEN
The causes of vasomotor symptoms, including hot flashes, are not fully understood, may be related to molecular factors, and have a polygenic architecture. Nutrients and bioactive molecules supplied to the body with food are metabolized using various enzymatic pathways. They can induce molecular cell signaling pathways and, consequently, activate effector proteins that modulate processes related to hot flashes in menopausal women. In this review, we analyzed the literature data from the last 5 years, especially regarding genome-wide association study (GWAS) analysis, and selected molecular factors and cell signaling pathways that may potentially be related to hot flashes in women. These are the kisspeptin-GnRH pathway, adipocyte-derived hormones, aryl hydrocarbon receptor signaling, catechol estrogens and estrogen sulfotransferase, inflammatory and oxidative stress biomarkers, and glucose availability. Then, single compounds or groups of food ingredients were selected that, according to experimental data, influence the course of the discussed molecular pathways and thus can be considered as potential natural therapeutic agents to effectively reduce the troublesome symptoms of menopause in women.
Asunto(s)
Estudio de Asociación del Genoma Completo , Sofocos , Femenino , Humanos , Sofocos/tratamiento farmacológico , Menopausia/fisiología , Hormonas/uso terapéutico , NutrientesRESUMEN
Background. The role of the transcribed ultra-conserved regions (T-UCRs) has not yet been fully discovered, but the studies showed some indications that impaired expression of T-UCRS were present in malignant tumors, including breast cancer. Aim. The presented work assessed the expression of two transcribed-ultra conserved regions−uc.63 and uc.38−in breast cancer tissue samples. Material and methods. The research was carried out on a group of 100 patients with invasive ductal carcinoma and 100 patients (test group) with benign tumors in breast tissue (control group). Results. As a result of the statistical analysis, it was shown that the expression of uc.63 and uc.38 is statistically significant, and, accordingly, higher (p < 0.0001) and lower (p < 0.0001) in the test group than in the control group. Statistical dependency analysis of the expression of uc.63 and uc.38 and the selected clinical and pathological factors showed that the expression of uc.63 statistically drops with the patient's age (p = 0.04), and is higher in the breast cancer tissue type M1 according to the TNM classification (p = 0.036) and in tissues with overexpressed HER2 (p = 0.035). Conclusion. The obtained results of the statistical analysis indicate a relationship between the expression of uc.63 and uc.38 and the occurrence of breast cancer.
Asunto(s)
Neoplasias de la Mama , ARN Largo no Codificante , Neoplasias de la Mama/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estadificación de Neoplasias , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
In this study, we retrospectively investigated GPER expression in biopsies of azoospermic men with complete (obstructive azoospermia-OA) and aberrant spermatogenesis (nonobstructive azoospermia-NOA). Each biopsy was histologically evaluated with morphometry. The testicular GPER expression was analyzed by the immunohistochemistry and RT-PCR technique in the whole testicular tissue and in seminiferous tubules and Leydig cells after laser-capture microdissection. In laser-microdissected compartments, we also analyzed transcriptional expression of selected Leydig (CYP17A1, HSD17B3, StAR) and Sertoli cell (AMH, SCF, BMP4) function markers. Immunohistochemical staining revealed expression of GPER in the cytoplasm of Leydig and Sertoli cells. Its stronger intensity was observed in Sertoli cells of NOA biopsies. The RT-PCR analysis of the GPER mRNA level unequivocally showed its increased expression in seminiferous tubules (i.e., Sertoli cells), not Leydig cells in NOA biopsies. This increased expression correlated positively with the transcriptional level of AMH-a marker of Sertoli cell immaturity, as well as FSH serum level in NOA but not in the OA group. Our results clearly demonstrate altered GPER expression in testes with primary spermatogenic impairment that might be related to Sertoli cell maturity/function.
RESUMEN
Genipin is an important monoterpene iridoid compound isolated from Gardenia jasminoides J.Ellis fruits and from Genipa americana fruits, or genipap. It is a precursor of a blue pigment which may be attractive alternative to existing food dyes and it possesses various potential therapeutic properties such as anti-cancer, anti-diabetic and hepatoprotective activity. Biomedical studies also show that genipin may act as a neuroprotective drug. This review describes new aspects of the bioactivity of genipin against various diseases, as well as its toxicity and industrial applications, and presents its potential mechanism of action.
Asunto(s)
Iridoides/química , Iridoides/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Color , Aditivos Alimentarios , Frutas/química , Humanos , Pigmentos Biológicos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacologíaRESUMEN
Propolis is a natural material that honey bees (Apis mellifera) produce from various botanical sources. The therapeutic activity of propolis, including antibacterial, antifungal, and anti-inflammatory effects, have been known since antiquity. Cancer is one of the major burdens of disease worldwide, therefore, numerous studies are being conducted to develop new chemotherapeutic agents and treatments for cancer. Propolis is a rich source of biologically active compounds, which affect numerous signaling pathways regulating crucial cellular processes. The results of the latest research show that propolis can inhibit proliferation, angiogenesis, and metastasis of cancer cells and stimulate apoptosis. Moreover, it may influence the tumor microenvironment and multidrug resistance of cancers. This review briefly summarizes the molecular mechanisms of anticancer activity of propolis and its compounds and highlights the potential benefits of propolis to reduce the side effects of chemotherapy and radiotherapy.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Própolis/química , Própolis/farmacología , Inductores de la Angiogénesis , Animales , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Antiinflamatorios/farmacología , Antifúngicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Abejas , Proliferación Celular/efectos de los fármacos , Humanos , Metástasis de la Neoplasia , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacosRESUMEN
Blue synthetic dyes are widely used in many industries. Although they are approved for use as food dyes and in cosmetics and some medicines, their impacts on consumer health remain unknown. Some studies indicate that 2 synthetic dyes, Blue No. 1 and Blue No. 2, may have toxic effects. It has therefore been suggested that these should be replaced with natural dyes; however, despite being nontoxic and arguably healthier than synthetic dyes, these compounds are often unsuitable for use in food or drugs due to their instability. Nevertheless, among the natural blue pigments, anthocyanins and genipin offer particular health benefits, as they are associated with the prevention of cardiovascular disease and have anticancer, neuroprotective, anti-inflammatory, and antidiabetic properties. This review summarizes the effects of blue food and drug colorings on health and proposes that synthetic colors should be replaced with natural ones.
Asunto(s)
Antocianinas , Colorantes , Antocianinas/farmacología , Alimentos , HumanosRESUMEN
OBJECTIVE: Epilepsy is a neurologically based disease. Literature data indicate a certain association between the polymorphism of these genes, which participate in the metabolism of drugs (CYP), and drug-resistant epilepsy. AIM: The reports describe studies in which an association was evaluated between the rs1799853 (430C > T) and rs1057910 (1075A > C) polymorphisms of CYP2C9 gene and the rs4244285 (c.681G > A) polymorphism of CYP2C19 gene on one hand and the incidence of drug-resistant epilepsy in children on the other. MATERIAL AND METHODS: The above-mentioned polymorphisms were assessed by the PCR-RFLP technique in a group of patients with drug-resistant (n = 106) and drug-responsive (n = 80) epilepsy, as well as in non-epileptic children (n = 97), all of them hospitalised at the Department of Neurology of the Institute-Polish Mother's Memorial Hospital in Lodz. RESULTS: It was demonstrated that CT genotype of the rs1799853 polymorphism of CYP2C9 gene and GA genotype of the rs4244285 polymorphism of CYP2C19 gene caused an enhanced risk of epilepsy. It was also shown that the occurrence of C-G-A haplotype, when referred to the rs1799853 polymorphism of CYP2C9 gene and the rs4244285 polymorphism of CYP2C19 gene, could be associated with a decreased risk of epilepsy occurrence. In case of the rs1799853 polymorphism in CYP2C9 gene, the occurrence of T allele four times increases the risk of drug-resistance in patients with diagnosed epilepsy. CONCLUSION: The obtained results indicated that the rs1799853 and rs1057910 polymorphisms of CYP2C9 gene and the rs4244285 polymorphism of CYP2C19 gene could be associated with the occurrence of drug-resistant epilepsy in children.
Asunto(s)
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Epilepsia Refractaria/epidemiología , Epilepsia Refractaria/genética , Niño , Femenino , Humanos , Masculino , Polonia/epidemiología , Polimorfismo de Nucleótido Simple , PrevalenciaRESUMEN
Saponins comprise a heterogenous group of chemical compounds containing a triterpene or steroid aglycone group and at least one sugar chain. They exist as secondary metabolites, occurring frequently in dicotyledonous plants and lower marine animals. Plant saponin extracts or single saponins have indicated antiplatelet and anticoagulant activity. Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism, is a multifactorial disease influenced by various patient characteristics such as age, immobility, previous thromboembolism and inherited thrombophilia. This mini-review (1) evaluates the current literature on saponins as modulators of the coagulation system, (2) discusses the impact of chemical structure on the modulation of the coagulation system, which may further provide a basis for drug or supplement design, (3) examines perspectives of their use in the prevention of VTE. It also describes the molecular mechanisms of action of the saponins involved in the prevention of VTE.
Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Saponinas/farmacología , Trombosis de la Vena/prevención & control , Animales , Ácido Araquidónico/metabolismo , Coagulación Sanguínea/fisiología , Humanos , Inhibidores de Agregación Plaquetaria/química , Inhibidores de Agregación Plaquetaria/farmacología , Glicoproteínas de Membrana Plaquetaria/metabolismo , Embolia Pulmonar/prevención & control , Saponinas/efectos adversos , Saponinas/química , Saponinas/uso terapéuticoRESUMEN
We investigated single nucleotide polymorphism (SNP) of the betaglycan gene (TGFBR3) encoding the TGFß co-receptor in endometrial cancer (EC) and its association with betaglycan expression. The study group included 153 women diagnosed with EC and 248 cancer-free controls. SNP genotyping and gene expression were analyzed using TaqMan probes. Three out of the eight SNPs tested, i.e., rs12566180 (CT; OR = 2.22; 95% CI = 1.15-4.30; p = 0.0177), rs6680463 (GC; OR = 2.34; 95% CI = 1.20-4.53; p = 0.0120) and rs2296621 (TT; OR = 6.40; 95% CI = 1.18-34.84; p = 0.0317) were found to be significantly associated with increased risk of EC (adjusted to age, body mass index, menarche and parity). Among the analyzed SNPs, only rs2296621 demonstrated the impact on the increased cancer aggressiveness evaluated by the WHO grading system (G3 vs. G1/2, GT-OR = 4.04; 95% CI = 1.56-10.51; p = 0.0026; T-OR = 2.38; 95% CI = 1.16-4.85; p = 0.0151). Linkage disequilibrium (LD) analysis revealed high LD (r2 ≥ 0.8) in two haploblocks, constructed by rs2770186/rs12141128 and rs12566180/rs6680463, respectively. In the case of C/C haplotype (OR = 4.82; 95% CI = 1.54-15.07; p = 0.0116-Bonferroni corrected) and T/G haplotype (OR = 3.25; 95% CI = 1.29-8.15; p = 0.0328-Bonferroni corrected) in haploblock rs12566180/rs6680463, significantly higher frequency was observed in patients with EC as compared to the control group. The genotype-phenotype studies showed that SNPs of the TGFBR3 gene associated with an increased risk of EC, i.e., rs12566180 and rs2296621 may affect betaglycan expression at the transcriptomic level (rs12566180-CC vs. TT, p < 0.01; rs2296621-GG vs. TT, p < 0.001, GT vs. TT, p < 0.05). Functional consequences of evaluated TGFBR3 gene SNPs were supported by RegulomeDB search. In conclusion, polymorphism of the TGFBR3 gene may be associated with an increased EC occurrence, as well as may be the molecular mechanism responsible for observed betaglycan down-regulation in EC patients.
RESUMEN
Beer is one of the most widely consumed alcoholic beverages in the world; however, traditional - and non-alcoholic beer consumption appear to have different effects on the cardiovascular system. In this short work, we review a base of recent papers to confirm whether, or not, moderate consumption of beer and its non-alcoholic components have a beneficial effect of cardiovascular system. Moreover, the present work reviews recently published papers regarding the influence of beer components on the hemostasis, cardiovascular system, and cardiovascular diseases (CVDs). Although most nutritional guidelines recommend a maximum of one beer per day for women and two for men, individual ideals may vary according to age, sex, genetics and body type, as well as drug or supplement use. Moreover, the recommendations for the moderate consumption of beer are often based on individual case reports and often small clinical experiments. In addition, as the health-related effects of beer consumption may also depend on the presence of other dietary components, as well as the type of beer, it is difficult to determine whether moderate consumption is universally safe and beneficial for the cardiovascular system. More randomized clinical trials are needed to determine this. Well-designed clinical trials are also required to determine the influence of various beer components on hemostasis and CVDs, and their effects in combination with drug or supplement therapy.
Asunto(s)
Cerveza , Enfermedades Cardiovasculares/fisiopatología , Hemostasis , HumanosRESUMEN
INTRODUCTION: Malignant neoplasm of the endometrium is the most common malignant neoplasm of the female reproductive system. Toll Like Receptors (TLR) play a significant role in innate and late-immunity against infections or damaged tissues. TLRs are also involved in the development of tumors in their natural microenvironment. TLRs play an important role in angiogenesis, necessary for survival and growth of the tumor. Hypoxia playing a critical role in angiogenesis, carcinogenesis, tumor progression and distant metastasis is primarily mediated through hypoxia inducible factors (HIFs). Vascular endothelial growth factor family proteins (VEGF) are also strongly involved in tumor angiogenesis and their action is strongly associated with TLR receptors. OBJECTIVES: The aim of the study was to correlate the expression of selected TLRs and VEGFR's as well as HIF1α with clinicopathological data of endometrial cancer patients. MATERIAL AND METHODS: 123 neoplastic endometrial samples were included in the study. 51 samples of healthy endometrium served as control. The expression of TLR1, TLR2, TLR3, TLR4, VEGFR1 and VEGFR2, VEGF-A and HIF1α was examined after RNA isolation at the mRNA level by Real Time-PCR. RESULTS: We have noted a significant correlation between the expression of selected TLR and VEGFR's and clinical stage as well as pathological grading of endometrial cancer. CONCLUSIONS: Received correlations confirm a significant contribution of some TLR expression and the receptor for VEGF in the pathogenesis of epithelial endometrial cancer.
Asunto(s)
Neoplasias Endometriales/metabolismo , Endometrio/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Transducción de Señal/fisiologíaRESUMEN
The exchange of metabolites between mitochondria and cytosol occurs through pores formed by voltage-dependent anion channel proteins. Voltage-dependent anion channels appear to be master regulators of mitochondrial bioenergetics and the intracellular flow of energy. Deregulation of voltage-dependent anion channels expression is thought to be related to mitochondrial dysfunction in cancer. The aim of this study was to investigate the mRNA and protein expression levels of VDAC1, VDAC2, and VDAC3 in relation to clinicopathological characteristics of endometrial cancer as well as the prognostic significance of voltage-dependent anion channels expression for overall survival. VDAC1 and VDAC3 expressions were significantly higher in cancer compared to normal tissues. Kaplan-Meier analysis indicated that high expression of all VDAC genes or high VDAC2 protein level predicted poor overall survival. Multivariate analysis identified the VDAC1 and VDAC2 mRNA levels as well as VDAC2 protein level as independent prognostic factors. Our results suggest that increased expression of voltage-dependent anion channels correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.
Asunto(s)
Neoplasias Endometriales/patología , Mitocondrias/patología , Proteínas de Transporte de Membrana Mitocondrial/genética , Canal Aniónico 1 Dependiente del Voltaje/genética , Canal Aniónico 2 Dependiente del Voltaje/genética , Canales Aniónicos Dependientes del Voltaje/genética , Secuencia de Aminoácidos , Biomarcadores de Tumor/genética , Citoplasma/metabolismo , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Mitocondrias/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/biosíntesis , Pronóstico , ARN Mensajero/genética , Canal Aniónico 1 Dependiente del Voltaje/biosíntesis , Canal Aniónico 2 Dependiente del Voltaje/biosíntesis , Canales Aniónicos Dependientes del Voltaje/biosíntesisRESUMEN
AIM: The analysis of oestrogen receptor (ESR2) and cytochrome P450 family 19 subfamily A member (CYP19A1) gene expression in the context of the risk for endometriosis development. MATERIALS AND METHODS: Tissue specimens, collected from patients with endometriosis (n=100) and from control patients (n=100) embedded into paraffin blocks, provided the material for genetic studies, oriented towards the expression of ESR2 and CYP19A1 genes. The gene expression was assessed by the reverse transcription-polymerase chain reaction technique. RESULTS: Higher expression levels of ESR2 gene were demonstrated in the patients with endometriosis in comparison with the healthy controls. The expression intensity of CYP19A1 gene was associated with endometriosis, manifested as abdominal wall nodules. A relationship was observed between CYP19A1 gene expression and the Revised American Society for Reproductive Medicine classification in the group with ovarian endometrioid cysts, as well as in the group with peritoneal endometriosis. CONCLUSION: This study suggests the significant role of ESR2 and CYP19A1 gene expression in the pathogenesis of endometriosis.
Asunto(s)
Endometriosis , Aromatasa/genética , Endometriosis/genética , Endometrio , Receptor beta de Estrógeno/genética , Femenino , Expresión Génica , Humanos , Regiones Promotoras GenéticasRESUMEN
OBJECTIVE: ESR2 and CYP19A1 genes play a major role in the hormonal control of women with endometriosis. The aim of the study was to analyze single nucleotide polymorphisms (SNPs) in the 3'UTR region of ESR2 and CYP19A1 genes. The study aimed at localisation of new polymorphisms, the nucleotide variants of which determine the level of susceptibility to endometriosis. STUDY DESIGN: The study included nâ¯=â¯200 patients: 100 with endometriosis and 100 healthy controls. The Sanger's sequencing method was applied for polymorphism analysis. RESULTS: Statistically significant correlations were identified between new, not previously described, two SNPs of ESR2 gene and endometriosis: rs4986938 (G>A) and rs928554 (A>G). In the case of rs4986938 polymorphism, the genotype AA was found to decrease the risk of endometriosis (ORâ¯=â¯0.24 95â¯% PU 0.05-1.22, p = 0.04). Analysis of the rs928554 polymorphism revealed that the occurrence of the AG genotype reduced the risk of endometriosis (OR = 0.38 95â¯% PU 0.21-0.71, p = 0.002). There were no differences in the distribution of genotypes of the polymorphisms rs10046 (C>T) and rs4646 (C>A) of CYP19A1 gene between patients and control. CONCLUSIONS: Further studies are necessary in groups with higher numbers of patients to explain whether the above-mentioned polymorphisms may be the risk factors for endometriosis.
Asunto(s)
Endometriosis , Regiones no Traducidas 3'/genética , Aromatasa/genética , Estudios de Casos y Controles , Endometriosis/genética , Receptor beta de Estrógeno/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
The most common cause of three major cardiovascular disorders, viz. ischemic heart disease (acute coronary syndrome), stroke and venous thromboembolism, is thrombosis. As blood platelets are considered the focal point of haemostasis, they play a key role in thrombosis and other cardiovascular diseases (CVDs). Various studies indicate that certain dietary components, such as phenolic compounds, selected vitamins (A and E) and unsaturated fatty acids, may act as important mediators in the prophylaxis and treatment of CVDs associated with platelet hyperactivation. It is possible that other components, such as natural and synthetic colourants may also possess such potential. Although studies have found individual food dyes or plant extracts acting as food colourants to demonstrate antiplatelet activity, no comprehensive and critical review has been performed of this activity. Therefore, the present paper reviews the current state of knowledge concerning the effect of colourants, especially natural ones, on blood platelet activity, as well as on thrombosis, being a consequence of platelet hyperactivation. It also discusses the molecular pathways of platelet activity as a basis for the development of effective antiplatelet therapies. The literature covered by this review suggests that such natural dyes can possess antiplatelet or anticoagulant activity; however, their antiplatelet action is complex and varies considerably, which may be attributed to differences in their chemical structure. Such natural food colourants may represent a promising alternative to synthetic food dyes.
Asunto(s)
Colorantes de Alimentos/farmacología , Colorantes de Alimentos/uso terapéutico , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , HumanosRESUMEN
The PI3K/AKT pathway is frequently activated in endometrial carcinoma. BMI-1 (B-lymphoma Mo-MLV insertion region 1) protein affects expression of PTEN (phosphatase and tensin homolog) in some cancers, but its significance for endometrial tumorigenesis is not known. The objective of this study was to determine the relationship between BMI-1 and expression of factors affecting AKT (protein kinase B) phosphorylation level in endometrial cancer. The expression of proteins and mRNAs was investigated in endometrial cancer specimens and samples of non-neoplastic endometrial tissue by Western blot and RT-PCR, respectively. The impact of BMI-1 down-regulation on AKT phosphorylation and expression of genes coding for several phosphatases were studied in HEC1A cells. The results showed that BMI-1 depletion caused increase in PHLPP1 and PHLPP2 (PH domain and leucine-rich repeat protein phosphatases 1/2) expression and decrease in phospho-AKT (pAKT) level. In more advanced tumours with higher metastatic potential, the expression of BMI-1 was lower compared to tumours less advanced and without lymph node metastasis. There were significant inverse correlations between BMI-1 and PHLPPs, especially PHLPP1 in normal endometrial samples. The inverse correlation between BMI-1 and PHLPP1/PHLPP2 expression was observed in PTEN positive but not PTEN negative cancers. Low PHLPP2 expression in tumours predicted poorer overall survival. BMI-1 impacts on AKT phosphorylation level in endometrial cells by regulation of PHLPP expression.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Endometriales/patología , Proteínas Nucleares/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Complejo Represivo Polycomb 1/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Proliferación Celular , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas Nucleares/genética , Fosfohidrolasa PTEN/genética , Fosfoproteínas Fosfatasas/genética , Fosforilación , Complejo Represivo Polycomb 1/genética , Pronóstico , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
Genetic polymorphisms in DNA repair genes may affect DNA repair efficiency and may contribute to the risk of developing cancer. The aim of our study was to investigate single nucleotide polymorphisms (SNPs) in RAD51 (rs2619679, rs2928140, and rs5030789) and XRCC3 (rs1799796) involved in DNA double-strand break repair and their relationship to prostate cancer. The study group included 99 men diagnosed with prostate cancer and 205 cancer-free controls. SNP genotyping was performed using the PCR-RFLP method. A significant association was detected between RAD51 rs5030789 polymorphism and XRCC3 rs1799796 polymorphism and an increased risk of prostate cancer. Our results indicate that RAD51 and XRCC3 polymorphism may contribute to prostate cancer.