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Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker. [ABSTRACT FROM AUTHOR]

ABSTRACT Ochratoxin A (OTA) is a highly toxic mycotoxin found worldwide in cereals, foods, animal feeds and different drinks. Based on previous studies, OTA is one of the major causes of the chronic tubulointerstitial nephropathy known as Balkan endemic nephropathy (BEN) and exerts several other adverse effects shown by cell and/or animal models. It is a well-known fact that OTA binds to various albumins with very high affinity. Recently, a few studies suggested that reducing the bound fraction of OTA might reduce its toxicity. Hypothetically, certain drugs can be effective competitors displacing OTA from its albumin complex. Therefore, we examined 13 different drug molecules to determine their competing abilities to displace OTA from human serum albumin (HSA). Competitors and ineffective chemicals were identified with a steady-state fluorescence polarization-based method. After characterization the competitive abilities of individual drugs, drug pairs were formed and their displacing activity were tested in OTA-HSA system. Indometacin, phenylbutazone, warfarin and furosemide showed the highest competing capacity but ibuprofen, glipizide and simvastatin represented detectable interaction too. Investigations of drug pairs raised the possibility of the presence of diverse binding sites of competing drugs. Apart from the chemical information obtained in our model, this explorative research might initiate future designs for epidemiologic studies to gain further in vivo evidence of long-term (potentially protective) effects of competing drugs administered to human patients. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

COPD (chronic obstructive pulmonary disease) is a chronic progressive inflammatory disease characterised by limitations in lung airflow that is not fully reversible. The concentrations and correlations of TNF-α, CXCL8, big ET-1 and hsCRP were investigated in healthy non-smokers, healthy smokers and patients with COPD in order to study their possible role in the pathophysiology of COPD. The concentrations of TNF-α, CXCL8 and big ET-1 were not statistically different between the experimental groups. No significant differences for the measured analytes were found between smokers and the non-smokers in the control group. The Spearman coefficient of correlation between the concentrations of TNF-α and CXCL8 was r = 0.638 (p<0.0001). However, the concentration of hsCRP was significantly higher in patients with COPD than in the control group (p = 0.0004). hsCRP proved to be a more sensitive diagnostic parameter than TNF-α, CXCL8 and big ET-1 in the systemic circulation in patients with COPD. [ABSTRACT FROM AUTHOR]

Individual and combined effects of the mycotoxins fumonisin B1, beauvericin and ochratoxin A on cell viability, lipid peroxidation (TBARS) and intracellular glutathione (GSH) were studied on porcine kidney epithelial cells (PK15). Cells were treated with 0.05, 0.5 and 5 µg/ml of each mycotoxin or the combinations of two or all three applied in equal concentrations for 24 and 48 hr. Changes in cell viability, GSH and TBARS levels showed that the cytotoxic effects of these mycotoxins were concentration- and time-dependent. After 24 hr, cell viability was significantly decreased by the exposure to 5 µg/ml of fumonisin B1 (25%), beauvericin (30%) and ochratoxin A (35%), as compared to controls. Only ochratoxin A (5 µg/ml) increased TBARS (56%), with further significant increase (85%) after 48 hr exposure. Fumonisin B1 and beauvericin significantly increased TBARS (57% and 80%, respectively) only when the highest dose was applied for 48 hr. After 24 hr, GSH was significantly decreased (18%) by ochratoxin A (0.05 µg/ml), whereas fumonisin B1 and beauvericin significantly decreased GSH at the concentration of 0.5 µg/ml. Combined treatment with fumonisin B1, beauvericin and ochratoxin A resulted mostly in additive effects especially after a 24-hr exposure, although synergistic as well as antagonistic interactions could not be excluded depending on toxin concentrations and time of exposure. This is the first report on beauvericin-induced effects on lipid peroxidation and GSH in animal cells. [ABSTRACT FROM AUTHOR]

Sepsis is a critical patient condition with high mortality rate caused by a complex and inadequate host response to infection. Since early identification and start of antibiotic therapy in the first few hours after sepsis development dramatically improves outcomes, it is of utter importance to offer fast, reliable and specific early laboratory biomarkers to help clinicians in sepsis recognition. On the other hand, the biomarkers should also be helpful in excluding sepsis and/or confirming therapy effectiveness, and thus prevent overprescribing of antibiotics. In this paper, we discuss the significance and relative merits of three currently available protein biomarkers: C-reactive protein, procalcitonin and presepsin. Although useful, none of these biomarkers has been shown to completely fulfill the roles mentioned above.

Ochratoxin A (OTA) is a highly toxic mycotoxin found worldwide in cereals, foods, animal feeds and different drinks. Based on previous studies, OTA is one of the major causes of the chronic tubulointerstitial nephropathy known as Balkan endemic nephropathy (BEN) and exerts several other adverse effects shown by cell and/or animal models. It is a well-known fact that OTA binds to various albumins with very high affinity. Recently, a few studies suggested that reducing the bound fraction of OTA might reduce its toxicity. Hypothetically, certain drugs can be effective competitors displacing OTA from its albumin complex. Therefore, we examined 13 different drug molecules to determine their competing abilities to displace OTA from human serum albumin (HSA). Competitors and ineffective chemicals were identified with a steady-state fluorescence polarization-based method. After characterization the competitive abilities of individual drugs, drug pairs were formed and their displacing activity were tested in OTA-HSA system. Indometacin, phenylbutazone, warfarin and furosemide showed the highest competing capacity but ibuprofen, glipizide and simvastatin represented detectable interaction too. Investigations of drug pairs raised the possibility of the presence of diverse binding sites of competing drugs. Apart from the chemical information obtained in our model, this explorative research might initiate future designs for epidemiologic studies to gain further in vivo evidence of long-term (potentially protective) effects of competing drugs administered to human patients., (Copyright © 2012 John Wiley & Sons, Ltd.)

Transformation of leukemic cells is associated with delay in maturation and in apoptosis, and to altered responsiveness to growth factors. However, some studies have revealed that Fas (CD95/APO1) which mediates apoptotic signal and decrease of anti-apoptotic Bcl-2 are frequently observed in acute myeloid leukemia (AML) M4/M5 leukemic cells. The aim of the study was to compare cytomorphology and cytochemistry of bone marrow (BM) apoptotic leukemic cells to preserved peripheral blood (PB) leukemic cells in our patient, a 76-year-old man with AML-M5b treated at Zagreb University Hospital Center. BM and PB of the AL patient were analyzed after Pappenheim and cytochemical stainings, and leukemic cells were classified according to FAB and WHO classification. Analysis of PB revealed leukocytosis and 80-90% monocytic cells (46% monoblasts, 29% promonocytes and 11% monocytes). Only a few preserved monoblasts and promonocytes were found in BM, together with numerous morphologically altered cells with characteristic chromatin condensation and pyknosis of nucleus, as well as nuclear fragmentation and formation of apoptotic bodies. Thus, cytomorphology of PB leukemic cells pointed to proliferation of immature monocytic cells, and cytomorphology of BM to cell apoptosis. Cytochemistry of PB monocytic cells and BM apoptotic cells confirmed monocytic cell lineage because esterase was strongly positive in almost all BM apoptotic leukemic cells and PB leukemic cells, and esterase was completely inhibited with sodium fluoride. On the basis of these findings, AML-M5b was diagnosed in our patient. There are many possible explanations for our observation of BM leukemic cell apoptosis in a patient with AML-M5. The most reliable one is that apoptosis was induced ex vivo after BM aspiration in course of the air drying of BM specimen before staining. Mass BM leukemic cell apoptosis that was recorded in contrast to numerous preserved leukemic cells in PK could be probably connected to unfavorable ratio of relatively low concentration of cytokines in relation to high leukemic cell number in BM aspirated cytologic specimen.

The toxicity of Ustilago maydis and the possible synergism with fumonisin B1 (FB1) were studied in Fischer rats by evaluating pathological changes and biochemical parameters in blood serum (LDH, ALT, GGT, ChE) and tissue homogenate of brain and liver (AChE, ChE, GGT, ALP). One experimental group (US) consumed diet with 70% of U. maydis galls and the other group (US+FB1) was fed pellets containing 70% of U. maydis galls and 1 mg of FB1 per kg of diet for 17 days. Control group (C) consumed standard pellets. During the trial, experimental animals were more excited, showing hyperactivity. Body mass gains slightly increased in both groups compared to the control. Gross pathological changes in liver, lungs, uterus and ovaries were more pronounced in the US+FB1 than in the US group. Specific catalytic activities of AChE decreased by 61% and by 63% in the liver and brain homogenate of the US group (p<0.05) compared to the control, indicating neurotoxic activity of U. maydis. Also, specific catalytic concentration of AChE and ALP was significantly decreased in the liver of the US+FB(1) group (p<0.05). Activity of LDH in the blood serum was increased up to 166% and 165% in the US+FB1 group (p<0.05) compared to the control and US group values, respectively, which indicates that FB1 was responsible for the disruption of cell membrane integrity. These findings suggest that Ustilago maydis and FB1 showed neurotoxicity in Fischer rats, which could be related to the alkaloids of U. maydis and disruption of sphingolipid metabolism by FB1 activity.