RESUMO
Research of the gut microbiota allows a better understanding of its composition and function and reveals the links between changes in the composition of bacteria and various intestinal but also systemic diseases. The gut microbiota performs several of important functions in the host body and influences many physiological processes. Gut bacteria synthesize many compounds needed for the proper function of the body (e.g., vitamins, short-chain fatty acids, and amino acids). They help maintain the integrity of the intestinal barrier and protect against pathogens. The gut microbiota plays a crucial role in the development and function of the immune system. Significant changes in the composition of the intestinal microbiota led to a dysbiotic state and the loss of its beneficial functions for humans. The review article summarizes the basic knowledge about the composition and function of the bacterial gut microbiota in healthy people, its role in the development of the immune system, and the mechanisms involved in maintaining homeostasis. It also presents current knowledge about the possibility of targeted modulation of the bacterial gut microbiota and faecal transplantation.
Assuntos
Microbioma Gastrointestinal , Humanos , Sistema Imunitário , Bactérias , Transplante de Microbiota FecalRESUMO
AIM of the study was to compare serum levels of IGF-1, IGF-2 and insulinlike growth factorbinding protein 3 (IGFBP-3) among nonobese and obese PCOS women, and to assess their relationship to metabolic and hormonal parameters. METHODS: The study included 64 women diagnosed with PCOS (age 28.9 ± 5 years); 30 of them with BMI > 27 and 34 with BMI lower than 27. All subjects were examined for parameters of glucose and lipid metabolism, steroid hormones and serum IGF-1, IGF-2 and IGFBP-3 levels. RESULTS: No significant differences in serum IGFBP-3 (p=0.534), IGF-1 (p=0.29) and IGF-2 (p=0.56) between two groups have been detected. IGFBP-3 was in positive correlation with total cholesterol (p=0.026), LDL cholesterol (p=0.03) and triacylglycerols (p=0.022). IGF-1 were negatively correlated with insulin (p=0.022), HOMA IR (p=0.033), triacylglycerols (p=0.0196) and waist circumference (p=0.049). A positive correlation was detected between IGF-1 and HDL cholesterol (p=0.025). No significant relationship was observed between IGF-1 and steroid hormones. CONCLUSION: Serum levels of IGF-1, IGF-2 and IGFBP-3 in obese PCOS women do not differ from those detected in nonobese PCOS women. IGF-1 negatively correlated with metabolic parameters, indicating that lower IGF-1 may represent an important predictor of metabolic syndrome (MS) in PCOS women. All peptides seem to have little effect on ovarian steroidogenesis in PCOS (Tab. 1, Fig. 1, Ref. 30).
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Síndrome do Ovário Policístico , Adulto , Índice de Massa Corporal , Feminino , Humanos , Insulina , Metaboloma , Obesidade , Adulto JovemRESUMO
BACKGROUND: A hundred years ago, scientists believed that amniotic fluid is a yellowish hypotonic mixture of foetal urine and maternal transudate with peculiar odour. Current knowledge shows that it represents a dynamic, complex mixture of inorganic and organic compounds. OBJECTIVES: Despite modern technological procedures, information is still lacking about the composition and properties of amniotic fluid. We focused on dynamics of selected physical and chemical properties of the amniotic fluid with the increasing gestational week. METHODS: The physicochemical characteristics of 89 amniotic fluid samples were determined according to the week of pregnancy. The determination of pH, specific gravity, glucose and nitrites was performed immediately, at room temperature. RESULTS: Our results show a significant negative correlation between week of pregnancy and semi-quantitative determined parameters of specific gravity (p < 0.001), pH (p < 0.01) and glucose (p < 0.001) values. Within the whole group of samples (n = 89), 29 % (n = 26) were nitrites positive (N+) and 71 % (n = 63) nitrites negative (N-). CONCLUSION: In this study were determined basic parameters of amniotic fluid, which could be related to a wide range of pathological states (Tab. 2, Fig. 1, Ref. 27).
Assuntos
Líquido Amniótico/metabolismo , Idade Gestacional , Glucose/metabolismo , Nitritos/metabolismo , Líquido Amniótico/química , Líquido Amniótico/fisiologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Gravidade EspecíficaRESUMO
The link between sunlight and skin cancer is a frequently discussed topic. However, ultraviolet radiation also induces the production of Vitamin D in the body. Keratinocytes and their ability to synthesize the active form of Vitamin D, which is consumed at the place of its origin in the skin, have a unique place in this discussion. We observe a remarkable sunshine-related paradox when we monitor the relationship between the dose of solar radiation and one type of skin cancer - malignant melanoma. Recent knowledge of the non-calcemic effects of Vitamin D, which include growth regulation, DNA repair, differentiation, apoptosis, membrane transport, metabolism, cell adhesion and oxidative stress, could help to further clarify this relationship. In this context, adjuvant Vitamin D therapy is currently being considered in patients with malignant melanoma, and this is expected to reduce tumor invasiveness and micrometastases and thus improve patient prognosis and reduce the risk of relapse.
Assuntos
Melanoma , Neoplasias Cutâneas , Vitamina D/fisiologia , Humanos , Queratinócitos/metabolismo , Recidiva Local de Neoplasia , Pele/metabolismo , Luz Solar , Raios Ultravioleta , Vitamina D/uso terapêuticoRESUMO
The incidence of malignant melanoma worldwide continues to grow despite the enormous advances in topical and systemic therapy. This increase is recorded regularly even in countries where, as a result of public health campaigns, dermatological examination and subsequent treatment have become more frequent. However, there have been reports of a stable or even decreasing mortality rate that seem to contradict the objective increase in its incidence. The well-known risk factors for malignant melanoma include sunburns and occasional sunbathing, whereas regular sunbathing is associated with a lower incidence. Besides DNA damage, exposure to the sun also results in the synthesis of vitamin D (cholecalciferol) in the skin, which contributes to over 90% of circulating Calcidiol (25 (OH) D) in serum. Current cultural norms (dressing, working indoors, avoiding sun exposure, and dietary choices) affect the serum vitamin D level, resulting in severely low serum levels of vitamin D in some sectors of todays society. Emerging data suggests that mild, unprotected exposure to UV radiation or dietary supplementation with oral vitamin D can reduce cancer mortality. Supplementation with vitamin D or alternatively UV exposure may be regarded as an adjuvant for the treatment of many types of tumors (e.g. tumors of the colon, prostate, and breast). The effect of vitamin D on malignant melanoma may be due to its non-calcemic systemic effects. Additionally, vitamin D may have more pronounced effects locally in the skin because of the unique ability of keratinocytes to synthesize the active form of vitamin D.Key words: malignant melanoma - vitamin D - adjuvant treatment therapy - clinical oncology The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 10. 2016Accepted: 26. 7. 2017.
Assuntos
Suplementos Nutricionais , Vitamina D , Humanos , Melanoma , Neoplasias Cutâneas , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Malignant melanoma is one of the most aggressive types of cancers. Melanoma is derived from pigment-producing cells, melanocytes, which are characterized by a specific survival mechanism. Microphthalmia-associated transcription factor (MITF-M) plays a role in the metabolism of melanoma and is involved in the regulation of the expression of multiple genes mediating processes such as melanogenesis, proliferation, differentiation, and melanocyte survival. The expression of this transcription factor in melanocytes is activated by several signaling pathways, and reduced expression or function of MITF-M can cause the dysregulation of anti-apoptotic mechanisms. MITF-M is also involved in matrix metalloproteinase 14 (MMP14) activity, which is responsible for shape changes in melanocytes and increases in their motility and invasiveness. Very low levels of expression of MITF-M are found in human melanocytes with an invasive phenotype, indicating that this transcription factor acts as a suppressor of the metastatic process. Cancer cells with low expression of cytosolic/nuclear ß-catenin have a small amount of MITF-M 14 that is insufficient to inhibit MMP transcription. The enzyme catalyzes the degradation of laminin and fibronectin, thereby changing the shape of melanocytes, which leads to their increased mobility and invasiveness. AIMS: This review describes the regulatory pathway of MITF-M activation, its involvement in the proliferation of transformed melanocytes, and its role in increasing the invasiveness of malignant melanoma. A detailed understanding of the MITF-M signaling pathway is highly topical and could help to develop new diagnostic and therapeutic applications for patients with malignant melanoma.Key words: neoplastic cell transformation - melanoma - MITF transcription factorThis work was supported by grant projects VEGA 1/0115/14 and VEGA 1/0873/16.The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 12. 2015Accepted: 14. 6. 2016.
Assuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Melanócitos/patologia , Melanoma/patologia , Fator de Transcrição Associado à Microftalmia/metabolismo , Humanos , Melanócitos/metabolismo , Melanoma/metabolismo , Invasividade Neoplásica , Transdução de SinaisRESUMO
Over the past few years, there has been evidence of the increasing prevalence of autoimmune diseases. Autoimmune diseases consist of many complex disorders of unknown etiology resulting in immune responses to self-antigens. The immune system, and its function, is under complex and integrated control and its disruption can be triggered by multiple factors. Autoimmunity development is influenced by multiple factors and is thought to be a result of interactions between genetic and environmental factors. Here, we review the role of a specific environmental factor, bisphenol A (BPA), in the pathogenesis of autoimmune diseases. BPA belongs to the group of environmental estrogens that have been identified as risk factors involved in the development of autoimmune diseases.
Assuntos
Autoimunidade , Compostos Benzidrílicos/efeitos adversos , Exposição Ambiental/efeitos adversos , Estrogênios não Esteroides/efeitos adversos , Fenóis/efeitos adversos , Animais , Autoantígenos/imunologia , Doenças Autoimunes/fisiopatologia , Compostos Benzidrílicos/imunologia , Estrogênios não Esteroides/imunologia , Humanos , Sistema Imunitário , Fenóis/imunologia , Fatores de RiscoRESUMO
Socioeconomic conditions and health of the Roma population, the most numerous minority in Europe, are worse than that of the non-Roma population. Information about the occurrence of human toxocarosis and other parasitic diseases in the Roma population is scarce or completely missing. The aim of this study was to map the seroprevalence of toxocarosis in the population living in segregated Roma settlements and to compare the data with the occurrence of antibodies in the non-Roma population of Eastern Slovakia. The seropositivity to Toxocara in 429 examined Roma inhabitants of segregated settlements reached 22·1%, while only 4/394 samples of the non-Roma population were found to be positive (odds ratio 27·7, P < 0·0001). Headache, muscle pain, influenza-like symptoms and diarrhoea occurred significantly more often in seropositive persons than in seronegative individuals. In the Roma population positivity was not influenced by gender, level of education and poverty, but age, lack of sanitary facilities and heating with wood significantly increased the risk of infection. It can be assumed that besides the high prevalence of toxocarosis, other parasitic diseases and communicable diseases will also be more prevalent in the Roma population living in segregated settlements.
Assuntos
Toxascaríase/epidemiologia , Toxocara/imunologia , Adolescente , Adulto , Animais , Estudos Transversais , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Soroepidemiológicos , Eslováquia/epidemiologia , Toxascaríase/patologia , Adulto JovemRESUMO
Ovarian cancer is the type of cancer with the highest mortality rate among gynaecologic malignancies. Due to lack of screening tools, this disease is mainly diagnosed at aâ¯progressed stage, when it is too late to adequate therapy. Despite many attempts, enough sensitive and specific biomarker was not still uncovered.â¯Fluorescence spectroscopy has proven to be aâ¯useful diagnostic tool with high efficiency. Fluorescence detection has three major advantages over other light-based investigation methods: high sensitivity, high speed, and reliability. Biological materials consist of aâ¯number of intrinsic fluorescent compounds -autofluorophores, which are associated with cardinal metabolic pathways. It is well known, that cancerous tissue metabolism is altered compared to healthy one, what influence also intrinsic fluorophores composition of bodily fluids. Urine is one of the biological fluids that could be obtained most easily and displays aâ¯blue - green fluorescence that can change in case of pathological process. Analysis of urine autofluorescence is non invasive and simple technique. Using fluorescent spectroscopy, ovarian cancer patients and healthy control group were discerned with high significance, so we predict that fluorescence analysis of urine could be aâ¯potential means of ovarian cancer screening.
Assuntos
Neoplasias Ovarianas/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluorescência , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Espectrometria de FluorescênciaRESUMO
BACKGROUND: Malignant melanoma is one of the most aggressive cutaneous tumors in men and women. The risk of developing a malignant melanoma depends on several external factors along with deregulation of mutual interaction of genotype and phenotype. Nowadays, growing attention is focused on the study of the interactions of the active form of vitamin D3 with its receptor and inhibitory effect of vitamin D3 receptor polymorphisms on multiple signaling pathways involved in proliferative and metastatic processes. OBJECTIVES: This review article addresses the relationship between factors involved in the development of malignant melanoma through Hedgehog signaling pathway (HH). It summarizes current knowledge of malignant melanoma in regard to the role of the active form of vitamin D3 binding to vitamin D3 receptor (VDR), as well as it describes the influence of polymorphisms of VDR on the inhibition of HH. Understanding of these mechanisms and critical assessment of available data is beneficial to both primary and secondary prevention of malignant melanoma particularly by means of chemoâ-preventive substances.
Assuntos
Melanoma/etiologia , Polimorfismo Genético , Receptores de Calcitriol/genética , Neoplasias Cutâneas/etiologia , Progressão da Doença , Feminino , Predisposição Genética para Doença , Proteínas Hedgehog/metabolismo , Humanos , Masculino , Melanoma/patologia , Fenótipo , Receptores de Calcitriol/metabolismo , Fatores de Risco , Transdução de Sinais , Neoplasias Cutâneas/patologia , Vitamina D/metabolismoRESUMO
BACKGROUND: Endometrial carcinoma (EC) is the most common cancer of the female reproductive tract in developed countries. The prognosis and 5-year survival rates are closely tied to the stage diagnosis. Current routine diagnostic methods of EC are either lacking specificity or are uncomfortable, invasive and painful for the patient. As of now, the gold diagnostic standard is endometrial biopsy. Early and non-invasive diagnosis of EC requires the identification of new biomarkers of disease and a screening test applicable to routine laboratory diagnostics. The application of untargeted metabolomics combined with artificial intelligence and biostatistics tools has the potential to qualitatively and quantitatively represent the metabolome, but its introduction into routine diagnostics is currently unrealistic due to the financial, time and interpretation challenges. Fluorescence spectral analysis of body fluids utilizes autofluorescence of certain metabolites to define the composition of the metabolome under physiological conditions. PURPOSE: This review highlights the potential of fluorescence spectroscopy in the early detection of EC. Data obtained by three-dimensional fluorescence spectroscopy define the quantitative and qualitative composition of the complex fluorescent metabolome and are useful for identifying biochemical metabolic changes associated with endometrial carcinogenesis. Autofluorescence of biological fluids has the prospect of providing new molecular markers of EC. By integrating machine learning and artificial intelligence algorithms in the data analysis of the fluorescent metabolome, this technique has great potential to be implemented in routine laboratory diagnostics.
Assuntos
Líquidos Corporais , Neoplasias do Endométrio , Humanos , Neoplasias do Endométrio/diagnóstico , Feminino , Líquidos Corporais/química , Biomarcadores Tumorais/análise , Espectrometria de Fluorescência/métodos , Detecção Precoce de Câncer/métodos , Metabolômica/métodos , Imagem Óptica , Inteligência ArtificialRESUMO
Multiple organ dysfunction syndrome (MODS) is characterized by the development of probably reversible, progressive dysfunction of vital systems in two or more organs, directly undamaged by surgery or other trauma. The organs which have the most common potential dysfunction are lungs, liver, kidneys, heart and gastrointestinal tract. The small intestine is the source of production of proinflammatory mediators leading and contributing to multiorgan failure. The endoplasmic reticulum (ER), after ischemia and post-ischemic reperfusion, is significantly involved in the activation of enterocyte apoptosis. The purpose of this study was to determine the stage of apoptosis in the lungs, initiated through inflammatory response from the small intestine. We analyzed changes in mRNA levels of pro-apoptotic genes Gadd153 (Chop) and anti-apoptotic genes Grp78 (Bip) in the small intestine wall and lung parenchyma. During experimental procedure the rats underwent 60 min of ischemia, caused by complete occlusion of the mesenteric arteria cranialis, with subsequent reperfusion and evaluation after 1 h, 24 h and 30 days (from R1, R24 to R30, respectively, each group n = 8). The gene expression levels were measured using RT-PCR followed by electrophoresis and visualization under UV. In the lungs we detected significantly lower level of expression Grp78 by 45 ± 6.9%. This suggests that ischemic attack and subsequent reperfusion did not promote ER stress in the lungs through induction of Gadd153 expression in the small intestine. There is still no effective approach to the treatment of affected ischemic intestine tissue, to stop the processes with could eventually lead to MODS. Therefore it is necessary to study changes in the damaged tissue at the molecular level and try to suggest possible therapeutic defined routes to the protection of tissue.
Assuntos
Apoptose , Retículo Endoplasmático/metabolismo , Proteínas de Choque Térmico/biossíntese , Intestino Delgado/metabolismo , Pulmão/patologia , Traumatismo por Reperfusão/metabolismo , Fator de Transcrição CHOP/biossíntese , Animais , Caspase 3/biossíntese , Catepsina B/biossíntese , Proteínas de Choque Térmico/genética , Intestino Delgado/patologia , Pulmão/metabolismo , Masculino , Artérias Mesentéricas/patologia , Oclusão Vascular Mesentérica/patologia , Chaperonas Moleculares/genética , Insuficiência de Múltiplos Órgãos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Fator de Transcrição CHOP/genéticaRESUMO
Bladder cancer is the fourth most common cancer in men and the eighth most common cancer in women. Oncomarkers play a crucial role in early detection of bladder cancer, as well as in treatment response monitoring and prognosis. Search for a new marker by molecular analysis is in progress because any diagnostic sensitivity and specificity enhancement is a great benefit for clinical practice.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Bexiga Urinária/diagnóstico , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Multiple sclerosis (MS) is a multifactorial disease that begins in 80-85% of patients as a relapsing-remitting form (RRMS), and about 50% of patients gradually develop a secondary progressive form (SPMS). Approximately 10-20% of patients are affected primarily by the progressive form (PPMS) of this disease, which is characterised by a progressive course. This work focuses on the detection of potential protein biomarkers (CHI3L1, sNfL, CXCL13, MCP-1, MMP-2, and MMP-9) in the serum of patients with multiple sclerosis, divided according to phenotype. PATIENTS AND METHODS: We detected serum (RRMS: n=40, SPMS: n=25, PPMS: n=15) concentrations of selected markers of demyelination and inflammation using ELISA and zymographic determination for accurate and reproducible recognition of individual forms of MS, as well as a comparison of their levels with a worsening of no evidence of disease activity (NEDA-3) status and patients' disability. RESULTS: We detected that concentrations of sNfL in the blood of patients with PMS were higher than in those with RRMS (about 46%, p<0.001). The association with a worsening of NEDA-3 status was confirmed in the RRMS group by positive correlation of sNfL and the expanded disability status scale (EDSS) score (r=0.579, p<0.01). The levels of MCP-1 protein were not significantly different in patients with the RRMS to the progressive form of MS (r=0.58, p=0.02), while the levels of CHI3L1 in both the RRMS and PMS groups were significantly increased in groups with evidence of disease activity (RRMS about 76%, p<0.001 and PMS about 62%, p<0.001). CONCLUSIONS: Earlier and non-invasive detection of serum biomarkers and their correlations with neurological disability can help to recognise the transition from RRMS to progressive forms of MS and complement the results of clinical and radiological follow-up of the patient and potentially help in monitoring the patient's response to the treatment.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Biomarcadores , Proteínas Sanguíneas , Progressão da Doença , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Recidiva Local de Neoplasia , FenótipoRESUMO
OBJECTIVE: We have evaluated the impact of chronic administration of clorgyline, a potent monoamine oxidase A inhibitor and a former antidepressant, on the preimplantation embryo development in Wistar rats. MATERIAL AND METHODS: Females were injected intraperitoneally daily for 30 days with saline (control animals, C), or with a low dose of clorgyline (0.1 mg/kg/day, LDC) or with a high dose of clorgyline (1 mg/kg/day, HDC). Embryos were isolated on day 5 of pregnancy and their urine was collected. RESULTS: The number of embryos per female did not differ between experimental groups and control, but we have recorded a decreased number of embryos in HDC group compared to LDC (p < 0.05). We have found that LDC significantly reduced the presence of healthy embryos and increased the presence of the degenerated embryos (p < 0.001). The administration of the LDC resulted in the lowest cell number in blastocysts (p < 0.01). Concerning monoamines in urine, we have observed significantly increased serotonin levels in HDC group compared to control (p < 0.05) and LDC animals (p < 0.01). Norepinephrine levels in both experimental groups were significantly elevated compared to controls, too (p < 0.001 LDC vs C; p < 0.01 HDC vs C). CONCLUSIONS: We assume that the impaired embryo development recorded in the LDC group after clorgyline administration was a consequence of the higher levels of the norepinephrine. We speculate that lesser negative effect of HDC compared to LDC on the preimplantation embryo development could be the consequence of the lesser norepinephrine levels and/or elevated serotonin levels (Tab. 2, Fig. 2, Ref. 37). Full Text in free PDF www.bmj.sk.
Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Norepinefrina/sangue , Serotonina/sangue , Animais , Clorgilina/farmacologia , Feminino , Inibidores da Monoaminoxidase/farmacologia , Gravidez , Ratos , Ratos WistarRESUMO
The causes of ovarian cancer have not been fully elucidated yet but genetic predisposition is found in approximately 10% of patients. When the disease is detected at an early stage, up to 90% of patients have a hope of recovery. However, no preventive measures or precise screening tests to detect early stages of this disease are known yet. Standard tumor markers (CA125) are usually investigated in women with an increased risk. Nevertheless, due to low sensitivity and specificity during the first stage of the cancer, CA125 determination showed a very low efficacy (less than 26%). There has been a considerable progress over the recent years in understanding the molecular mechanisms leading to tumor formation and metastasis. Gradually, 46 genes were identified, initially named tumor endothelial markers (TEM), the expression of which is increased in tumors compared to normal endothelial cells. Death receptor 6 (DR6) and glycoprotein M6B (GPM6B), both detectable from patients serum, are among the most promising candidates for a marker of an early stage of ovarian cancer. This review aims to clearly describe potential as well as clinically used tumor markers useful in an early detection of ovarian cancer. Search for new markers, characterized by increased expression in patients'blood is a highly topical issue.
Assuntos
Neoplasias Ovarianas/diagnóstico , Biomarcadores Tumorais/sangue , Diagnóstico Precoce , Feminino , HumanosRESUMO
Urine contains a variety of organic and inorganic chemicals including a number of natural fluorophores. Most of them are formed by tryptophan metabolites. But there are also metabolites of riboflavin, catecholamines and porphyrins. The alternation in the autofluorescence of urine and the alternation in the concentration of these substances are developed by both physiological and pathological changes such as disorder of body metabolism, dietary intake, age and etc. In this work we present fluorescent properties of chosen urine fluorophores - i.e. 5-hydroxyindole-3-acetic acid (5-HIAA), indoxyl sulphate (urine indican), serotonin (5-HT), vanillylmandelic (VMA) and homovanillic (HVA) acids typical for various diseases. Differences of fluorescent parameters of individual fluorophores measured in vitro in the water solutions and in natural environment of urine are significant and can lead to false results and conclusions. Therefore, we present the most common influence that can occur in urine (e.g. pH, ionic strength, proteins, and other fluorophores). The aim is to elaborate the exact "know-how" for direct complex fluorescent measurement in urine related to particular diagnoses.
Assuntos
Espectrometria de Fluorescência , Urina/química , Biomarcadores/urina , Ácido Homovanílico/urina , Humanos , Ácido Hidroxi-Indolacético/urina , Indicã/urina , Serotonina/urina , Ácido Vanilmandélico/urinaRESUMO
Analysis of changes after ischemia-reperfusion (IR) attack to the small intestine leads to multiple organ dysfunction (multiple organ dysfunction syndrome, MODS) and the subsequent death of patients is a topic for discussion. IR stress affects the endoplasmic reticulum (ER). ER dysfunction induces responses through kinases activation that stimulate anti-apoptotic mechanism, for example Grp78 (Bip) (Yeung et al., 2008) and pro-apoptotic mechanism, for example, activation Gadd153 (Chop) (Allyson et al., 2007). We analyzed the impact of IR damage of epithelium of the small intestine of rats after 1 h ischemia and subsequent 1 h, 24 h and 30 days of reperfusion on the level of apoptotic genes expression (Gadd153) and (Bip). In this study we used RT-PCR for detection of changes in gene expression. Significantly increased levels of mRNA for Gadd153 gene were detected after 1 h ischemia and 1 h reperfusion. The mRNA level of Grp78 gene was increased 24 h after ischemia comparing with the control groups. After 30 days of reperfusion Grp78 was at the level of control groups. Still, it is necessary to analyze the changes in the damaged tissue at the molecular level to define possible pathways leading to the tissue protection.
Assuntos
Apoptose/genética , Expressão Gênica , Proteínas de Choque Térmico/genética , Intestino Delgado/irrigação sanguínea , Traumatismo por Reperfusão/genética , Fator de Transcrição CHOP/genética , Animais , Chaperona BiP do Retículo Endoplasmático , Intestino Delgado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismoRESUMO
Adrenal incidentalomas (AI) are very common and mostly they are non-functioning adenomas (NFA). NFAs are often associated with insulin resistance and metabolic syndrome. Several biomarkers, including certain growth factors, may participatein the pathogenesis ofmetabolic changes in patients with adrenal adenomas.Patients with NFA and age-matched control subjects were enrolled in the study. Data on age, gender, presence of metabolic syndrome or its components were obtained for each subject. Blood samples were obtained and glycemia, insulinemia, lipid profile, and selected growth factor levels were measured. Forty-three patients with NFA and 40 controls were included in the study. Differences were not found in the metabolic syndrome and its components prevalence or in the biochemical profile between patients and the control group. Significant differences were noticed in the levels of IGF1, IGF2, and IGFBP3 (p=0.016, p=0.005, p=0.004, respectively), but there were no differences in VEGF or EGF concentrations. In NFA patients, an association between glycemia and EGF levels was present (p=0.026). No significant correlations between tumor size and insulin or growth factor concentrations were present in AI patients. Significantly higher serum IGF1, IGF2, and IGFBP3 concentrations in NFA patients may support the role of the IGF axis in the pathogenesis of adrenocortical lesions.No correlation between IGFs or IGFBP3 and parameters of glucose or lipid metabolism was found. Present results may support the role of the growth hormone axis rather than hyperinsulinemia and insulin resistance in the pathogenesis of adrenocortical adenomas.
Assuntos
Neoplasias do Córtex Suprarrenal/sangue , Adenoma Adrenocortical/sangue , Fator de Crescimento Epidérmico/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Adenoma Adrenocortical/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
OBJECTIVE: Malignant melanoma (MM), as well as other cancers, is a disorder in the cell life cycle at many levels. In terms of energy, the sync of cytosolic and mitochondrial metabolism is required for each cell. Mismatches also caused by hypoxic factors accumulate defects leading to the formation, development and invasiveness of malignant melanoma. Our aim was to compare the effect of HIF-1α and miR-210 on the metabolism of malignant melanoma cells in normoxia and pseudohypoxia. Further, we also investigated how gene silencing affects the viability in order to evaluate the potential of gene therapy in the treatment of MM. MATERIALS AND METHODS: We targeted oxidative phosphorylation by genetically suppressing HIF-1α and miR-210. We have examined mitochondrial activity, cytosolic glycolysis and cell viability. RESULTS: The ratio of NADH/NAD+ in the cytoplasm under normal conditions is stable and can thus serve as a specific cellular metabolic marker. Therefore, the study was aimed at finding the cause of the reduction in NADH levels in increasing hypoxia under ideal in vitro conditions on the SK-MEL-30 malignant melanoma cells. The relationship between HIF-1α and miR-210, their effect on transcriptional level, and the subsequent effect on metabolic process attenuation in cells was investigated. Obtained results indicate that the NADH which is accumulated by cells in hypoxia was significantly decreased upon gene silencing. CONCLUSIONS: Our studies have shown that small regulatory molecules with organelle-specific effect (such as miRs) need to be targeted, and that the resultant effect is comparable to silencing of "general" hypoxic transcription factors.