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The campaign to promote the natural feeding of infants, at least for the first six months of life, conducted over recent years has deep justification from a medical point of view. Numerous gynecological and pediatric societies around the world recommend breastfeeding as the most appropriate way of feeding infants. It has been proven that the benefits of this type of nutrition go beyond nutritional aspects, proper growth and development. The list of long-term metabolic benefits, which include reducing the incidence of obesity, allergies, infections and diabetes, is constantly growing. It has been shown that the method of feeding infants using various mechanisms may influence the tendency of the liver to accumulate fatty compounds and develop fatty liver disease with its metabolic consequences leading to liver failure, cirrhosis and hepatocellular carcinoma. This is an important discovery due to the growing obesity epidemic in adults and children. Metabolic dysfunction - associated fatty liver disease (MAFLD) has become the most common cause of chronic liver disease, affecting 25% of the global population. The results of studies conducted in recent years have shown the protective effect of breastfeeding on the risk of developing MAFLD later in life in both children and breastfeeding women. New scientific reports provide the basis for qualifying breastfeeding as a modifiable risk factor for MAFLD.
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Interconnections between hypothyroidism and metabolic disturbances manifesting in the liver and body composition have not yet been comprehensively analyzed in the context of lifestyle. This study aimed to assess the selected lifestyle factors and quality of life in the context of the development of NAFL (non-alcoholic fatty liver) in women diagnosed with hypothyroidism. This study included 134 women categorized into three groups: with hypothyroidism and NAFL, with only hypothyroidism, and with only NAFL. We compared the groups concerning the KomPAN and WHOQOL-BREF questionnaires, anthropometric measurements, body composition parameters, and the stage of liver steatosis. The individuals with NAFL most frequently consumed lard, fried dishes, processed meats, red meat, sweets, and sweetened beverages. The individuals with hypothyroidism without coexisting NAFL exhibited the highest satisfaction with health. The NAFL group had the highest average body fat percentage. Selected lifestyle aspects influenced the development of NAFL in women diagnosed with hypothyroidism. Women's overall quality of life did not vary depending on the coexisting medical conditions. Preventive programs should promote the following: the regular consumption of meals, the appropriate energy supply, physical activity, mental health support, and striving for proper body composition parameters.
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Non-alcoholic fatty liver disease (NAFLD) is a global problem. It may be caused by metabolic and hormonal disorders, including hypothyroidism. However, non-thyroid causes of NAFLD in people with hypothyroidism, including improper eating behavior and low physical activity, should be acknowledged. This study aimed to present the current literature on whether the development of NAFLD is related to hypothyroidism or a typical consequence of an unhealthy lifestyle in people with hypothyroidism. The results of previous studies do not allow for an unequivocal determination of the pathogenetic relationship between hypothyroidism and NAFLD. Important non-thyroid-initiating factors include providing too many calories in relation to requirements, consuming excessive amounts of monosaccharides and saturated fats, being overweight, and maintaining low physical activity levels. The recommended nutritional model for both hypothyroidism and NAFLD may be the Mediterranean diet, which is rich in fruits and vegetables, polyunsaturated fatty acids, and vitamin E.
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This study aimed to assess the magnitude of anti-SARS-CoV-2 immunoglobulin G (IgG) titers and Interferon-Gamma Release Assay (IGRA) test results following administration of booster BNT162b2 in 48 ChAd-primed participants (vaccination schedule: ChAd/ChAd/BNT). Whole blood samples were collected: first, before and second, 21 days after the booster dose. The IgG level was measured using chemiluminescent immunoassay; the intensity of the T-cell response-IFNγ concentration-was assessed using IGRA test. At 21 days after the booster, all subjects achieved reactive/positive anti-SARS-CoV-2 IgG, and IGRA test results showed a significant increase compared to the results before booster administration. We compared the results before and after the booster between participants with and without prior history of COVID-19. The IFNγ concentrations in both cohorts were higher in convalescents (both before booster and 21 days after). The IgG titers were subtly lower in COVID-19 convalescents than in naïve but without statistical significance. Data on cell-mediated immunity are scarce, especially with regard to the general population. A better understanding of the complexity of the immune response to SARS-CoV-2 could contribute to developing more effective vaccination strategies.
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Tumor cells stimulate local angiogenesis, resulting in their further multiplication and spread. Angiogenesis is a multifaceted process in which angiopoietins parti- cipate. Angiopoietin-1 (Ang-1) through its receptor Tie2 stimulates endothelial cell survival and the maintenance of the endothelial barrier. These phenomena can support tumour growth by promoting angiogenesis. On the other hand, overproduction of Ang-1 triggers endothelium stability and can lead to angiogenesis inhibition. Because of the ambiguous role of Ang-1, we decided to determine its clinical significance in patients with resectable NSCLC. In a group of 47 patients, tumours and the adjacent non-cancerous tissues were assessed for ANG-1 mRNA expression (using Q-RT-PCR analysis) and Ang-1 concentration (by enzyme-linked immunosorbent assay) together with clinical parameters and the five-year survival rate. ANG-1 expression and Ang-1 concentration were higher in tumour-free tissue, showing no differences between histological types of NSCLC, clinical stage or grading and seemed not to determine the five-year survival. ANG-1 expression and Ang-1 concentration in tumour and tumour-free tissues in patients with NSCLC seem not to be useful as factors supporting either diagnostics or prognosis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Angiopoyetina 1/genética , Angiopoyetina 2/genética , Angiopoyetina 2/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neovascularización Patológica , Pronóstico , Receptor TIE-2/genética , Receptor TIE-2/metabolismoRESUMEN
BACKGROUND: The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients. AIM: To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting. METHODS: The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis. RESULTS: During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy. CONCLUSION: In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR.
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Enfermedad Hepática en Estado Terminal , Hepatitis C Crónica , Neoplasias Hepáticas , Antivirales/efectos adversos , Niño , Estudios de Cohortes , Quimioterapia Combinada , Enfermedad Hepática en Estado Terminal/tratamiento farmacológico , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Polonia , Índice de Severidad de la Enfermedad , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
Lung tissue is directly exposed to high oxygen pressure, as well as increased endogenous and exogenous oxidative stress. Reactive oxygen species (ROS) generated in these conditions play an important role in the initiation and promotion of neoplastic growth. In response to oxidative stress, the antioxidant activity increases and minimizes ROS-induced injury in experimental systems. The aim of the present study was to evaluate the activity of antioxidant enzymes, such as superoxide dismutase (SOD; isoforms: Cu/ZnSOD and MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST), along with the concentration of malondialdehyde (MDA) in tumor and adjacent noncancerous tissues of two histological types of NSCLC, i.e., adenocarcinoma and squamous cell carcinoma, collected from 53 individuals with surgically resectable NSCLC. MDA concentration was similar in tumors compared with adjacent noncancerous tissues. Tumor cells had low MnSOD activity, usually low Cu/ZnSOD activity, and almost always low catalase activity compared with those of the corresponding tumor-free lung tissues. Activities of GSH-related enzymes were significantly higher in tumor tissues, irrespective of the histological type of cancer. This pattern of antioxidant enzymes activity could possibly be the way by which tumor cells protect themselves against increased oxidative stress.
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Antioxidantes/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Neoplasias Pulmonares/enzimología , Proteínas de Neoplasias/metabolismo , Oxidorreductasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana EdadRESUMEN
AIM OF THE STUDY: Chronic hepatitis C (CHC) is a viral disease with metabolic disturbances involved in its pathogenesis. Adipokines may influence the inflammatory response and contribute to development of metabolic abnormalities in CHC. Visfatin exerts immunomodulatory and insulin-mimetic effects. The aim was to measure visfatin serum concentrations and its mRNA hepatic expression in non-obese CHC patients and to assess the relationships with metabolic and histological parameters. MATERIAL AND METHODS: In a group of 63 non-obese CHC patients (29 M/34 F) infected with genotype 1b aged 46.6 ±14.6 years, body mass index (BMI) 24.8 ±3.0 kg/m2, serum visfatin levels and its mRNA hepatic expression were examined and the subsequent associations with metabolic and histopathological features were assessed. RESULTS: Serum visfatin levels were significantly higher in CHC patients compared to controls (22.7 ±5.7 vs. 17.8 ±1.5 ng/ml, p < 0.001). There was no difference in serum visfatin and its mRNA hepatic expression regardless of sex, BMI, insulin sensitivity and lipids concentrations. There was no mutual correlation between serum visfatin and visfatin mRNA hepatic expression. Hepatic visfatin mRNA levels but not visfatin serum levels were higher in patients with steatosis (1.35 ±0.75 vs. 0.98 ±0.34, p = 0.009). CONCLUSIONS: Serum visfatin levels may reflect its involvement in chronic inflammatory processes accompanying HCV infection. Increased visfatin mRNA hepatic expression in patients with steatosis seems to be a compensatory mechanism enabling hepatocytes to survive metabolic abnormalities resulting from virus-related lipid droplet deposition prerequisite to HCV replication.
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BACKGROUND: According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs. ledipasvir/sofosbuvir±RBV (LSR) in PI-experienced patients in real-life setting. METHODS: Our analysis included patients registered in the nationwide, investigators initiated, multicentre EpiTer-2 database. Among 4530 patients registered, 335 with genotype 1 (93% 1b) were previously treated with IFN-based regimens with PIs: 127 with boceprevir (BOC), 208 with telaprevir (TVR). Patients with advanced fibrosis (F3/F4) were significantly predominant (BOC 28.4%/61.4%, TVR 18.8%/64.4%, respectively). Subjects were assigned to IFN-free retreatment as follows: BOC - 64 (50.4%) PrODR and 63 (49.6%) LSR; TVR- 103 (49.5%) PrODR and 105 (50.5%) LSR. RESULTS: SVR rates were comparable for particular groups: BOC â PrODR- 100%; BOC â LSR - 98%; TVR â PrODR - 97%; TVR â LSR - 96% (intent-to treat analysis-ITT) and BOC â PrODRâ100%; BOC â LSR - 99%; TVR â PrODR - 99%; TVR â LSR - 98% (modified intent-to treat analysis-mITT). Both treatment regimens had a favourable safety profile. Adverse events (AEs) were generally mild or moderate in severity. Three deaths were reported. The treatment was stopped due to AEs in five patients (three treated with PrODR and two with LSR). CONCLUSION: Efficacy and safety of treatment with PrODR and LSR is comparable in BOC or TVR-experienced patients.
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Anilidas/administración & dosificación , Bencimidazoles/uso terapéutico , Carbamatos/administración & dosificación , Farmacorresistencia Viral Múltiple/efectos de los fármacos , Fluorenos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Macrocíclicos/administración & dosificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Uracilo/análogos & derivados , Uridina Monofosfato/análogos & derivados , 2-Naftilamina , Adulto , Anciano , Anilidas/efectos adversos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Carbamatos/efectos adversos , Estudios de Cohortes , Ciclopropanos , Quimioterapia Combinada , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Humanos , Interferones/administración & dosificación , Interferones/efectos adversos , Lactamas Macrocíclicas , Compuestos Macrocíclicos/efectos adversos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Prolina/análogos & derivados , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/efectos adversos , Ritonavir/efectos adversos , Sofosbuvir , Sulfonamidas/efectos adversos , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/efectos adversos , Uridina Monofosfato/uso terapéutico , Valina , Adulto JovenRESUMEN
OBJECTIVE: Introduction: In recent years, interests on dietary and health food have grown considerably. Nutritional knowledge and eating habits determined in the youth have an impact on the health condition in adulthood. The aim: To evaluate the eating habits in the population of young people from Silesian province. PATIENTS AND METHODS: Materials and methods: The anonymous questionnaire survey was conducted in the group of high school students aged 17-21 years coming from Silesian province, randomly chosen from high schools in Ruda Slaska. The study group consisted of 262 students, 157 (59,9%) women and 105 (40,1%) men. The student`s participation in the study was voluntary. RESULTS: Results: The analysis showed that as many as 40% of high school students never eat regularly and eating of regular meals reported only 11,5%. Less than a half (46,9%) of participants eat breakfast every day. The most commonly consumed meals was lunch (n = 217; 82,8%) and dinner (n = 143; 54,6%). The vast majority of students (77,5%) didn't know the correct classification of the feeding pyramid floors. Moreover, in more than a half of young women (54,8%) and men (52,4%) the body mass deficiency was revealed (BMI<18kg/m2). CONCLUSION: Conclusions: The study showed abnormal nutritional behavior of high school youth. Therefore, there is a need to conduct activities under health prevention, which improve the eating habits of young people.
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Dieta/estadística & datos numéricos , Conducta Alimentaria/psicología , Preferencias Alimentarias/psicología , Conductas Relacionadas con la Salud , Estado Nutricional , Adolescente , Dieta/psicología , Femenino , Humanos , Masculino , Polonia , Distribución por Sexo , Estudiantes/estadística & datos numéricos , Adulto JovenRESUMEN
The study evaluates the influence of steatosis on hepatocytes proliferative potential, reflected by proliferating cell nuclear antigen (PCNA) expression in chronic hepatitis C (CHC) patients both in steatotic and non-steatotic areas of lobules. The liver histology was evaluated according to Kleiner's score. Nonalcoholic steatohepatitis (NASH) was also defined as the presence of lobular inflammation, hepatocyte ballooning and steatosis. Expression of PCNA was significantly in patients with definite NASH compared to those with simple steatosis, but not to those with borderline NASH. Advanced steatosis negatively influenced PCNA expression. NASH not only affects PCNA expression in staetotic, but also in non-steatotic lobule areas. Expression of PCNA could be an independent indicator of changes in hepatocyte metabolism in CHC patients. High NAS values and low PCNA expression may be a negative prognostic factor in predicting the further course of the disease.
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Hepatitis C Crónica/patología , Hepatocitos/citología , Enfermedad del Hígado Graso no Alcohólico/patología , Proliferación Celular , Humanos , Inflamación , HígadoRESUMEN
Telomerase, undetectable in normal somatic cells, plays a critical role in carcinogenesis of the majority of human tumors including lung carcinoma. The aim of our study was to determine human telomerase reverse transcriptase (hTERT) mRNA expression in patients with non-small cell lung cancer (NSCLC) in order to estimate its usefulness as diagnostic and/or prognostic factor. hTERT expression was analyzed in a group of 12 females and 28 males with NSCLC using Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR method) in cancerous and non-cancerous lung tissues. Results were analyzed according to clinical data and one-, two-, and five-year survival rates. hTERT expression in the cancerous tissue was significantly higher than in the lung parenchyma free from neoplasm infiltration (p<0.05). There was no significant association between hTERT expression in the tumor tissue and age, gender, grading or clinical stage. A significant difference in hTERT expression between two types of histopathological patterns (adenocarcinoma and squamous cell carcinoma) was detected (p=0.01). No association between hTERT expression in NSCLC specimens and survival rates was found. hTERT mRNA detection by QRT-PCR in tumor and corresponding cancer-free tissues can be used as a diagnostic marker in patients with NSCLC, but seems not to be a prognostic factor.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Telomerasa/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Liver regeneration is a complex, highly coordinated process which can be disturbed by the impact of the anti-proliferative interferon α activity. In the model of partial hepatectomy (PH) in the rat the expression of HGF and EGF genes and their molecules' tissue concentrations were analyzed in the later stages of liver regeneration (48-120 h). MATERIAL AND METHODS: 40 three-month-old male Wistar rats were randomized to groups of 20 animals each. The rats of the study group (IFN/H) were injected subcutaneously with IFNα-2b, while the control group was injected with 0.5 ml of 0.9% NaCl (NaCl/H). In the liver tissue samples obtained during hepatectomy and autopsy (regenerating liver mass) the expression of HGF and EGF genes was estimated with the Q-PCR method and the analysis of HGF and EGF molecule concentrations in tissue homogenates was conducted with the ELISA method. RESULTS: HGF but not EGF expression was significantly higher at 48 h after PH, while EGF expression was higher in normal than in regenerating liver tissue at 120 h. The analyses of correlations between expression of HGF and EGF in regenerating liver tissue, both normal and upon IFNα-2b influence, together with correlations between those factors genes' expression and HGF and EGF tissue concentrations in analyzed samples, showed no significant differences. CONCLUSIONS: HGF and EGF are not significantly involved in regulation of later stages of rat liver regeneration. IFNα-2b does not impact expression of their genes or the presence of these growth factor molecules in regenerating liver tissue.
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Chronic hepatitis C (CHC) is accompanied by numerous metabolic disorders, partially associated with altered adipokine system regulation. Omentin (intelectin-1) is a novel adipokine known to play a pivotal role in metabolic regulation in CHC. In a group of 63 CHC patients (29 men/34 women) infected with genotype 1b, aged 6.6 ± 14.6 years, serum omentin levels and its gene expression in liver tissue were examined and their association with metabolic and histopathological features was assessed. Serum omentin levels were significantly higher in CHC patients compared to controls (p < 0.001), regardless of sex, body mass index (BMI), insulin sensitivity and lipid concentrations. There was no correlation between serum omentin and omentin hepatic expression. Neither parameter was associated with any histological features. Serum omentin in non-obese CHC patients seems not to be related to metabolic disorders or liver pathology. Omentin hepatic expression shows no relationship with either serum omentin levels or histopathological features. This suggests different mechanisms regulating circulating omentin concentration and omentin hepatic expression in CHC.
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Citocinas/biosíntesis , Hepatitis C Crónica/metabolismo , Lectinas/biosíntesis , Adulto , Anciano , Citocinas/análisis , Femenino , Proteínas Ligadas a GPI/análisis , Proteínas Ligadas a GPI/biosíntesis , Hepatitis C Crónica/patología , Humanos , Lectinas/análisis , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
INTRODUCTION: Chemerin seems to be involved in pathogenesis of chronic hepatitis C (CHC). Hepatic expressions of chemerin and its receptor, chemokine receptor-like 1 (CMKLR1), in CHC have not been studied so far. AIM: To evaluate chemerin and CMKLR1 hepatic expression together with serum chemerin concentration in CHC patients and to assess their relationship with metabolic and histopathological abnormalities. METHODS: The study included 63 nonobese CHC patients. Transcription of chemerin and CMKLR1 was assessed by quantitative real-time PCR, while serum chemerin was assessed by enzyme-linked immunosorbent assay. RESULTS: Expression of chemerin and CMKLR1 was present in the liver of all CHC patients regardless of sex or age. This expression was not associated with necroinflammatory activity and steatosis grade, fibrosis stage, and metabolic abnormalities. There was a negative association between serum chemerin and chemerin hepatic expression (r = (-0.41), P = 0.006). CONCLUSION: The study for the first time confirmed a marked expression of chemerin and CMKLR1 in the liver of CHC patients. The study was performed using the homogenates of human liver tissue, so it is not possible to define whether hepatocytes or other cell types which are abundantly represented in the liver constitute the main source of chemerin and CMKLR1 mRNA.
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Quimiocinas/metabolismo , Hepatitis C Crónica/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Hígado/metabolismo , Receptores de Quimiocina/metabolismo , Índice de Masa Corporal , Estudios de Casos y Controles , Quimiocinas/sangre , Femenino , Regulación de la Expresión Génica , Hepatitis C Crónica/sangre , Hepatitis C Crónica/genética , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Péptidos y Proteínas de Señalización Intercelular/sangre , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most abundant oxidatively modified lesions in DNA and is a marker of the oxidative stress. 8-OHdG is a mutagenic lesion and it can mispair with adenine, causing G:CâT: A transversion. Our task was to determine the 8-OHdG level in patients with colorectal adenocarcinoma directly in tumor tissues and corresponding normal mucosa. MATERIAL/METHODS: Samples of tumor tissues and corresponding normal mucosa of 47 patients undergoing surgery for colorectal cancer were analyzed. DNA was isolated from both tumor and normal tissues. Then, DNA was hydrolyzed to nucleotides using nuclease P1 and alkaline phosphatase. The 8-OHdG and 2'-dG (2'-deoxyguanosine) were determined in hydrolysates by high-performance liquid chromatography (HPLC) with electrochemical (EC) and UV detector. RESULTS: The levels of 8-OHdG in colorectal adenocarcinoma tissues were higher than in corresponding normal mucosa. No significant differences were shown in 8-OHdG levels in the cancerous and cancer-free tissues between age and sex and stages A/B and C/D of Duke's classification. CONCLUSIONS: 8-OHdG reflects the local oxidative stress in colon adenocarcinoma tissue together with ageing processes, but not the intensity of tumorigenesis itself. Because of many factors that could influence the oxidative modification of DNA bases, its role as a diagnostic and/or prognostic factor in colon adenocarcinoma seems to be limited.
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Adenocarcinoma/metabolismo , Neoplasias Colorrectales/metabolismo , ADN/análisis , Desoxiguanosina/análogos & derivados , Estrés Oxidativo/fisiología , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Cromatografía Líquida de Alta Presión , Desoxiguanosina/análisis , Femenino , Humanos , Masculino , Polonia , Estadísticas no ParamétricasRESUMEN
Oxidative stress is one of several factors which contribute to the development of colorectal carcinogenesis. The aim of the study was an assessment of the activity of antioxidant enzymes in tumour and corresponding normal distal mucosa in a group of patients with colorectal adenocarcinoma. Samples of tumour and corresponding normal mucosa were obtained during a resection of colorectal cancer from 47 patients aged between 26 and 82 years. The average distance of corresponding normal distal mucosa from the tumour was 4.49 cm. Activities of antioxidant enzymes: superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione S-transferase (GST), and catalase (CAT) were measured in tissue homogenates. The patients were grouped according to the tumour stage (Duke's staging), grading, localization, and size of tumour, as well as age and sex. Statistical analysis was performed. The activity of SOD and GPx was considerably increased, while the activity of GST decreased significantly in tumour as compared with normal mucosa. GR activity in colorectal cancer was evidently higher in tumours of proximal location compared with the distal ones. The distance of corresponding normal distal mucosa from the tumour was analyzed and related to all assayed parameters. A decreased GST activity was observed in corresponding normal mucosa more than 5 cm distant from the tumour in patients with CD Duke's stage. The higher activity of superoxide dismutase and glutathione peroxidase in tumour compared to corresponding normal mucosa could indicate higher oxidative stress in colorectal adenocarcinoma cells.
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Adenocarcinoma , Neoplasias Colorrectales , Membrana Mucosa/metabolismo , Estrés Oxidativo , Adenocarcinoma/enzimología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antioxidantes , Catalasa/metabolismo , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Helicobacter pylori colonizes the human gastric mucosa, leading to chronic superficial gastritis and in some cases to peptic ulceration, gastric adenocarcinoma, or gastric lymphoma. It has been postulated that the clinical outcome depends on differences in H. pylori strain virulence as well as on individual factors of the host. Thus, we aimed to assess the relation between H. pylori cagA/vacA genotypes and the TNF-alpha gene expression in gastric mucosa specimens from patients with chronic gastritis. MATERIAL/METHODS: This study was conducted with gastric mucosa samples obtained during gastroendoscopy from 43 H. pylori-infected individuals with chronic gastritis. The presence of ureA and cagA genes and vacA allele combinations were analyzed in isolated DNA by the polymerase chain reaction method. Isolates of RNA were used for cDNA synthesis by reverse transcription. Synthesized cDNA was used to determine the TNF-alpha gene expression level by quantitative real-time polymerase chain reaction assay. RESULTS: The cagA gene was detected in 67.44% of H. pylori strains. Five vacA alleles in the tested H. pylori strains were detected: s1a/m1 (18.60%), s1a/m2 (23.26%), s1a/m3 (18.60%), s1b/m2 (6.98%), and s2m2 (32.56%). There were no significant differences in TNF-alpha gene expression in strains expressing cagA versus those not expressing this gene, and no significant differences among strains with different vacA alleles. CONCLUSIONS: TNF-alpha gene expression in the gastric mucosa of H. pylori-infected patients appears to be independent of H. pylori cagA/vacA genotype.
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Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Factor de Necrosis Tumoral alfa/genética , Adulto , Anciano , Alelos , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Factor de Necrosis Tumoral alfa/metabolismo , VirulenciaRESUMEN
BACKGROUND: Colorectal cancer, one of the most aggressive cancers, occurs with a high incidence in most countries. The usual treatment is surgery and subsequent chemotherapy and radiotherapy. Cancer development and progression is dictated by series of alterations in genes such as tumor suppressor genes, DNA repair genes, oncogenes and others. In colorectal carcinogenesis disturbances different from mutations called an epigenetic regulation are also taken into consideration. Epigenetics is defined as a modifications of the genome, heritable during cell division, which do not involve a change in the DNA sequence. In our study we analyzed methylation of CpG islands in the MGMT and p16 genes in sporadic colorectal cancers and normal corresponding colonic mucosa. MATERIAL/METHODS: Fresh tissue samples were obtained from 68 patients (age of 23 to 81 years) with primary colorectal adenocarcinoma and corresponding normal tissues. We used methylation-specific polymerase chain reaction (MSP) for analysis of the methylation status of MGMT and p16. RESULTS: Methylation of MGMT and p16 was detected in 59% and 53% of tumors, respectively. In corresponding normal colonic mucosa methylation of MGMT was detected in 20% and p16 in 18%. The normal colon mucosa obtained from younger patients (age of <65 years) showed less methylation frequency as compared with the normal mucosa from the older ones (age of >65 years). CONCLUSIONS: The older age and female gender are generally associated with higher methylation levels for most CpG islands in normal colonic mucosa. These results indicate that MGMT and/or p16 aberrant methylation may play an important role in colorectal cancer.
Asunto(s)
Colon/anatomía & histología , Neoplasias Colorrectales/genética , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Genes p16 , Mucosa Intestinal/anatomía & histología , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Anciano de 80 o más Años , Colon/patología , Neoplasias Colorrectales/patología , Islas de CpG , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Epigénesis Genética , Femenino , Humanos , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas , Proteínas Supresoras de Tumor/metabolismo , Adulto JovenRESUMEN
Forestry workers are a group of a high risk of occupational exposure to tick-borne diseases. The group of 51 healthy persons with a history of more than 3 years forestry working was tested for antibodies against B. burgdorferi and tick-borne encephalitis (TBE) and reviewed on tick-bites preventive methods usage. Two-steps serological examination revealed the anti-B. burgdorferi antibodies in 14 (27.5%) persons. Anti-TBE antibodies were present in 6 (11.8%) persons. Despite of multiple tick bites in anamnesis, methods of ticks bites prevention (clothes, repellents) were used by less than 30% of workers. Similarly, anti-TBE vaccination was conducted only in 11 persons. Concluding, the elaboration of educational, prophylactic and efficacy monitoring standards for this occupational group is needed.