The association of microRNAs in the development of retinopathy of prematurity.

INTRODUCTION: Retinopathy of prematurity (ROP) is one of the main reasons of preventable childhood blindness. In the development of ROP, MicroRNAs may be effective in the balance of factors that inhibit and activate angiogenic factors. We aimed to determine the changes in the blood levels of miR-146a, miR-143, miR-210, miR-21, miR-126, miR-211, miR-221, miR-106 and let 7f and to investigate their association with ROP. We hypothesed that the level of these miRNAs changed significantly in ROP cases. MATERIALS AND METHODS: This observational study was conducted prospectively in preterm infants with ROP. Serum levels of 8 miRNAs were measured. The relationship between disease stage and progression with miRNA gene expression was analysed. Preterm infants without ROP were taken as the control group. RESULTS: 47 patients with ROP and 14 controls, were included in the study. In the ROP group, miR-210, miR-146a, miR-21 were statistically significantly lower. In the ROP group the expression level of miR-143 was insignificantly lower, miRNA-221 was insignificantly higher, and miR-106, miR-126 and let 7f were variable. CONCLUSION: It was observed that miR-210, miR-146a, miR-21 and miR-143 were significantly lower in patients with ROP compared to the control group. However, no association could be established between the type of miRNA and stage of ROP. These miRNAs may be used as adjunctive biomarkers for diagnosis of ROP.

Physiological aspect of apoptosis-regulating microRNAs expressions during fasting.

OBJECTIVE: Fasting is an activity that requires a certain calorie restriction without consuming food or drinks for a certain period of daytime. However, fasting triggers many complex events, including activating cellular stress response pathways, autophagy promotion, apoptosis pathways, and a change in hormonal balance. Among the many events affecting the regulation of apoptosis, the expression of microRNAs (miRNAs) plays an important role. Therefore, we aimed to investigate the levels and importance of miRNA expression in fasting. PATIENTS AND METHODS: The expressions of 19 miRNAs regulating different pathways from saliva samples, isolated by matching healthy university students (n = 34) as group 1 (fasting for 17 consecutive hours) and group 2 (testing 70 minutes after meal consumption), were examined using the real-time PCR method. RESULTS: In fasting, modulation of apoptotic pathways by miRNAs triggers anti-pathogenic effects, and the adaptation of abnormal cells in the body decreases. For this reason, vital diseases, such as cancer, can be treated by preventing the proliferation and growth of cancerous cells by increasing programmed cell death due to the downregulation expression mechanism of miRNAs. CONCLUSIONS: Our study aims to improve the knowledge about the mechanisms and functions of miRNAs in various apoptosis pathways during fasting and may be a model for further future physiological and pathological studies.

A New Promising Pathway in Aggressive Prostate Cancer: Treg/mir-let8c/lin28b

Purpose: The progress of prostate cancer entails complex contemporaneous tumor developmental events in diverse stages that they are still yet to be clarified. miRNAs might accompany to balance between regulatory and cytotoxic T cells in tumors. Here, we investigated miRNAs and Regulatory T cell (Treg) marker FOXP3 expressions within prostate cancer spectrum. Methods: Thirty-eight prostate cancer patients enrolled within two groups to the study as having Gleason Score ≤ 7 (Group-1) and ≥ 8 (Group-2) that compared to 19 benign prostate hyperplasia controls. Twelve miRNAs expressions were analyzed by real time PCR from paraffin-embedded prostate tissue samples. Correlations between serum PSA levels, immunohistochemical staining of CD3, CD4, FOXP3 and miRNA expressions were analyzed. Results: In our study, hsa-let7c-3p significantly 1,52 (p=0.018) and 1,84 (p=0.0095) fold down- regulated whereas, miR-141-3p was significantly 2,36 (p=0.0006) and 2,24 (p=0.001) fold upregulated in the prostate cancer patients compared to benign prostate hyperplasia in group 1 and 2, respectively. Only CD4 (p=0.004) and PSA (p<0.001) have statistically significant differences among groups when compared to benign prostate hyperplasia. miR-143-p, miR-221-3p, hsa-let7c-3p and miR-17-3p expressions were significantly correlated with regulatory T cell marker FOXP3 expression. Conclusions: For the first time, we reported significantly altered expression levels of miRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143, miR17) and correlations between Treg marker FOXP3 in the aggressive prostate cancer patients suggesting that prostate cancer progression might be under the regulation of crosstalk between Tregs and miRNAs (AU)

Propósito: El progreso del cáncer de próstata implicaeventos complejos de desarrollo tumoral contemporáneo endiversas etapas que aún no se han aclarado. Aquí, investigamos los MIRNAs y el marcador de células T reguladoras(Treg) FOXP3 expresiones dentro del espectro de cáncer depróstata.Métodos: Treinta y ocho pacientes con cáncer depróstata inscritos dentro de dos grupos para el estudio unapuntuación de Gleason ≤ 7 (Grupo-1) y ≥ 8(Grupo-2)que en comparación con 19 controles benignos de hiperplasia de próstata. Doce expresiones miRNAs fueron analizadas por PCR en tiempo real a partir demuestras detejidoprostático incrustado en parafina. Se analizaronlos nivelesde PSA séricos de correlaciónsetween, la tinción inmunohistoquímica de expresiones CD3, CD4, FOXP3 y miRNA.Resultados: En nuestro estudio, has-let7c-3p significativamente 1,52 (p-0.018) y 1,84 (p-0. 0095) plegarsehacia abajo, mientras que, miR-141-3p fue significativamente 2,36 (p-0.0006) y 2,24 (p-0. 001) plegarse reguladoen los pacientes con cáncer de próstata en comparación conla hiperplasia benigna de próstata en los grupos 1 y 2, respectivamente. Sólo CD4 (p-0.004) y PSA (p<0. 001)tienen diferencias estadísticamente significativas entre losgrupos en comparación con la hiperplasia benigna de próstata. las expresiones miR-143-p, miR-221-3p, has-let7c-3py miR-17-3p se correlacionaron significativamente conlaexpresión FOXP3 del marcador de celda T egulatorio r.Conclusiones: Fo laprimera vez,informamos denivelde expresión significativamente alterado demiRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143,miR17) y correlaciones entre el marcador Treg DE Treg33en los pacientes agresivos de cáncer de próstata sugiriendoque la progresión del cáncer de próstata podría estar bajo laregulación de la cruz entre Tregtalks y miR. (AU)

Increased oxidative stress in patients with essential thrombocythemia.

BACKGROUND: Essential thrombocythemia (ET) is a clonal disease in which thrombotic and hemorrhagic complications are common. Our aim in this study was to investigate whether oxidative stress in ET patients increased compared to healthy volunteers and to investigate whether there is a relationship between vascular events and oxidative status parameters in ET patients. PATIENTS AND METHODS: We determined the serum levels of oxidative status parameters, such as total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) in ET patients. Forty-three ET patients (20 males, 23 females) and 20 healthy volunteers were enrolled. Oxidative status parameters of the patients were compared with those of the controls at time of diagnosis and at 6th-month follow-up. Additionally, oxidative status parameters of patients with ET with a history of vascular event were compared with patients without a vascular event history during diagnosis. RESULTS: Rises in TOS, OSI, and MDA were statistically significant in the patients group; however, the TAS value was significantly lower compared to the control group. Furthermore, TOS was significantly higher in patients with history of vascular event compared to the patients without such a history. Following therapy, OSI and MDA values were significantly reduced in the patient group compared to the pre-treatment values. CONCLUSIONS: Our findings reveal that although oxidative stress parameters were increased, compensative total antioxidant status was significantly reduced in ET patients. Furthermore, TOS values were significantly high in patients with a history of vascular event.

Preventive and protective effects of Turkish propolis on H2O2-induced DNA damage in foreskin fibroblast cell lines.

The aim of the present study was to evaluate the potential of Turkish propolis extracts if they prevent or protect foreskin fibroblast cells against hydrogen peroxide (H2O2)-induced oxidative DNA damage. Hydrogen peroxide (40 µM) was used as an inducer of oxidative DNA damage. The damage of DNA was evaluated by using the alkaline single cell gel electrophoresis (comet) assay. Turkish propolis extracts at concentrations of 25, 50, 75 and 100 µg/ml were prepared by ethanol. Anti-genotoxicity was assessed before, simultaneously, and after treatment of propolis extract (50 µg/ml) with H2O2. The results showed a significant decrease in H2O2-induced DNA damage in cultures treated with propolis extract. The antioxidant activity of phenolic components found in propolis may contribute to reduce the DNA damage induced by H2O2. Our findings confirmed the chemopreventive activity of propolis and showed that this effect may occur under different mechanisms.

Effects of imatinib mesylate on renin-angiotensin system (RAS) activity during the clinical course of chronic myeloid leukaemia.

The renin-angiotensin system (RAS) is involved in cell growth, proliferation and differentiation in bone marrow in an autocrine-paracrine manner, and it modulates normal and neoplastic haematopoietic cell proliferation. This study aimed to assess expressions of the RAS components, renin, angiotensinogen and angiotensin-converting enzyme (ACE), during imatinib mesylate treatment of patients with chronic myeloid leukaemia (CML). Expressions of RAS components were studied in patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and these expression levels decreased following administration of imatinib. The RAS activities were significantly different among Sokal risk groups of CML, highlighting the altered biological activity of RAS in neoplastic disorders. The results of this study confirm that haematopoietic RAS affects neoplastic cell production, which may be altered via administration of tyrosine kinase inhibitors such as imatinib mesylate.

Novel chromosomal translocations in multiple myeloma: t(13;16)(q14;q24) and t(1;15)(q10;q26).

Multiple myeloma (MM) is a malignant plasma cell disorder that involves multiple genetic abnormalities. Chimeric transcription factors, created by gene fusion as a result of chromosomal translocations, have been implicated in the pathogenesis of the disease. Here, we report the conventional cytogenetic analysis of a MM patient that showed a complex set of novel chromosomal rearrangements, including t(13;16)(q14;q24) and t(1;15)(q10;q26). This is probably the result of fusion of previously known genes, and would contribute to prognostic significance of the disease.

A novel Fryns "Anophthalmia-plus" syndrome associated with primary hypothyroidism.

A novel Fryns "anophthalmla-plus" syndrome associated with primary hypothyroidism: Here, we report a newborn male with "anophthalmia-plus" syndrome and primary congenital hypothyroidism. To our knowledge this is the first case of 'anophthalmia-plus' syndrome associated with congenital hypothyroidism in the literature up to date.

Why hepatocellular carcinoma cells are unlikely to metastasize: is there a role for tissue inhibitor of metalloproteinase-1?

The question 'Why hepatocellular carcinoma cells are unlikely to metastasize although they have a high proliferative activity?' is a major point of interest from a cancer physiopathological viewpoint. Recent articles about the roles and relationships of some cytokines with matrix degrading enzymes and their inhibitors in various types of normal tissues and malignancies give rise to another question: 'Does tissue inhibitor of metalloproteinase-1 prevent the extrahepatic metastasis of hepatocellular carcinoma cells?' On the basis of many evidences, it is highly probable that under the effect of a possible inducing mechanism of the cytokines interleukin-6, -1 beta and transforming growth factor beta, the increase in concentration of tissue inhibitor of metalloproteinase-1 in hepatocellular carcinoma cause increased type I collagen accumulation and consequent prevention of cellular detachment, which explains why highly proliferative malignant hepatocytes have less metastatic ability.

Is there a relationship between tissue inhibitor of metalloproteinase-1 and transforming growth factor-beta 1 with respect to malignant melanoma progression?

Recent articles about the roles and relationships of tissue inhibitor of metalloproteinase-1 and transforming growth factor-beta 1 in various types of normal tissues and malignancies give rise to the question: 'Is there a relationship between them with regard to malignant melanoma progression?' In the light of many references, it seems to be highly probable that the tissue inhibitor of metalloproteinase-1, -- being a multifunctional protein -- functions as a growth factor with possible stimulation by transforming growth factor-beta 1 in progression of malignant melanoma, rather than its other existing functions in many different normal and cancer tissues (e.g. inhibition of the matrix metalloproteinases or functioning as an insignificant inhibitor of angiogenesis).