Advances in microRNAs as Emerging Biomarkers for Colorectal Cancer Early Detection and Diagnosis.

Colorectal cancer (CRC) remains the second most common cause of cancer-related mortality worldwide, necessitating advancements in early detection and innovative treatment strategies. MicroRNAs (miRNAs), small non-coding RNAs involved in gene regulation, have emerged as crucial players in the pathogenesis of CRC. This review synthesizes the latest findings on miRNA deregulated in precancerous lesions and in CRC. By examining the deregulation patterns of miRNAs across different stages of CRC development, this review highlights their potential as diagnostic tools. We specifically analyse the roles and diagnostic relevance of four miRNAs-miR-15b, miR-21, miR-31, and miR-146a-that consistently exhibit altered expression in CRC. The current knowledge of their role in key oncogenic pathways, drug resistance, and clinical relevance is discussed. Despite challenges posed by the heterogeneity of the research findings on miRNA deregulation and their role in CRC, integrating miRNA diagnostics into current screening methods holds promise for enhancing personalized medicine approaches. This review emphasizes the transformative potential of miRNAs in CRC diagnosis, paving the way for improved patient outcomes and novel therapeutic paradigms.

Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82 years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

Fractal characterization of retinal microvascular network morphology during diabetic retinopathy progression.

OBJECTIVE: The study aimed to characterize morphological changes of the retinal microvascular network during the progression of diabetic retinopathy. METHODS: Publicly available retinal images captured by a digital fundus camera from DIARETDB1 and STARE databases were used. The retinal microvessels were segmented using the automatic method, and vascular network morphology was analyzed by fractal parametrization such as box-counting dimension, lacunarity, and multifractals. RESULTS: The results of the analysis were affected by the ability of the segmentation method to include smaller vessels with more branching generations. In cases where the segmentation was more detailed and included a higher number of vessel branching generations, increased severity of diabetic retinopathy was associated with increased complexity of microvascular network as measured by box-counting and multifractal dimensions, and decreased gappiness of retinal microvascular network as measured by lacunarity parameter. This association was not observed if the segmentation method included only 3-4 vessel branching generations. CONCLUSIONS: Severe stages of diabetic retinopathy could be detected noninvasively by using high resolution fundus photography and automatic microvascular segmentation to the high number of branching generations, followed by fractal analysis parametrization. This approach could improve risk stratification for the development of microvascular complications, cardiovascular disease, and dementia in diabetes.

The pterygopalatine fossa: morphometric CT study with clinical implications.

PURPOSE: The pterygopalatine fossa is a deep viscerocranial space containing the maxillary artery and nerve, the pterygopalatine ganglion, and the nerve of the pterygoid canal (vidian nerve). The endoscopic approach to this area relies on adequate preoperative imaging, such as computed tomography (CT). The aim was to determine the morphometric characteristics of the pterygopalatine fossa and its communications, including several previously unpublished measurements. METHODS: 100 CT scans (56 male and 44 female patients) were analyzed. The axial, coronal, and sagittal slices, together with the three-dimensional reconstructions, were used in the study. RESULTS: The central diameter and the length of the foramen rotundum, the vertical diameter and the length of the pterygoid (vidian) canal, and the diameter of the sphenopalatine foramen were significantly larger in men. The central diameters of the foramen rotundum and the vidian canal were significantly smaller than their anterior and posterior transverse diameters. The vidian canal length of 12.1 mm indicates the presence of the type 3 VC with a sensitivity of 83% and a specificity of 85%. CONCLUSION: Several new descriptions of the pterygopalatine fossa are presented here (such as the angle between the sphenopalatine foramen and the vidian canal, a new aspect in the understanding of the FR, and the distance between the posterior wall of the maxillary sinus to the vidian canal and the foramen rotundum), which might prove useful in the comprehension of the anatomy of the pterygopalatine fossa.

Fractal dimension and lacunarity analysis of retinal microvascular morphology in hypertension and diabetes.

Hypertension and diabetes mellitus represent modifiable risk factors for vascular disease. They cause microvascular remodeling, and ultimately result in end-organ damage. Therefore, development of methods for noninvasive quantification of the effects of hypertension and diabetes mellitus on microvasculature is of paramount importance. The two goals of the study were: 1) to characterize the geometric complexity and inhomogeneity of retinal vasculature in hypertensive retinopathy (HR) and in proliferative diabetic retinopathy (PDR) by using box counting fractal dimension and lacunarity analysis, and 2) to determine if the combination of these two parameters can be used to describe differences in the vascular tree geometry between HR and PDR. The extended set of retinal images from the publicly available STARE database was manually segmented by our expert, validated, and made available for other researchers to use. The healthy retinal vascular network has a higher complexity (fractal dimension) compared to that in HR and in PDR. However, there is no difference in microvascular complexity between HR and PDR. The inhomogeneity of the retinal microvascular tree (lacunarity) was higher in PDR compared to HR. Lacunarity and fractal dimension together quantitatively characterize microvascular geometry in the retina with higher specificity than fractal analysis alone.

Oral teicoplanin versus oral vancomycin for the treatment of severe Clostridium difficile infection: a prospective observational study.

The aim of this study was to compare clinical cure rate, recurrence rate and time to resolution of diarrhea in patients with severe and severe-complicated Clostridium difficile infection (CDI) treated with teicoplanin or vancomycin. This two-year prospective observational study included patients with first episode or first recurrence of CDI who had severe or severe-complicated CDI and were treated with teicoplanin or vancomycin. Primary outcomes of interest were clinical cure rate at discharge and recurrence rate after eight weeks follow up, and secondary outcomes were all-cause mortality and time to resolution of diarrhea. Among 287 study patients, 107 were treated with teicoplanin and 180 with vancomycin. The mean age of patients was 73.5 ± 10.6 years. One hundred eighty six patients (64.8%) had prior CDI episode. Severe complicated disease was detected in 23/107 (21.5%) and 42/180 (23.3%) patients treated with teicoplanin and vancomycin, respectively. There was no statistically significant difference in time to resolution of diarrhea between two treatment arms (6.0 ± 3.4 vs 6.2 ± 3.1 days, p = 0.672). Treatment with teicoplanin resulted in significantly higher clinical cure rate compared to vancomycin [90.7% vs 79.4%, p = 0.013, odds ratio (OR) (95% confidence interval (CI)) 2.51 (1.19-5.28)]. Recurrence rates were significantly lower in patients treated with teicoplanin [9/97 (9.3%) vs 49/143 (34.3%), p < 0.001, OR (95%CI) 0.20 (0.09-0.42)]. There was no statistically significant difference in overall mortality rate. Teicoplanin might be a good treatment option for patients with severe CDI. Patients treated with teicoplanin experienced remarkably lower recurrence rates compared to vancomycin-treated patients.

Atrial fibrillation is associated with the fibrotic remodelling of adipose tissue in the subepicardium of human and sheep atria.

AIMS: Accumulation of atrial adipose tissue is associated with atrial fibrillation (AF). However, the underlying mechanisms remain poorly understood. We examined the relationship between the characteristics of fatty infiltrates of the atrial myocardium and the history of AF. METHODS AND RESULTS: Atrial samples, collected in 92 patients during cardiac surgery and in a sheep model of persistent AF, were subjected to a detailed histological analysis. In sections of human right atrial samples, subepicardial fatty infiltrations were commonly observed in the majority of patients. A clear difference in the appearance and fibrotic content of these fatty infiltrations was observed. Fibro-fatty infiltrates predominated in patients with permanent AF (no AF: 37 ± 24% vs. paroxysmal AF: 50 ± 21% vs. permanent AF: 64 ± 23%, P < 0.001). An inverse correlation between fibrotic remodelling and the amount of subepicardial adipose tissue suggested the progressive fibrosis of fatty infiltrates with permanent AF. This hypothesis was tested in a sheep model of AF. In AF sheep, an increased accumulation of peri-atrial fat depot was observed on cardiac magnetic resonance imaging and dense fibro-fatty infiltrations predominated in the left atria of AF sheep. Cellular inflammation, mainly consisting of functional cytotoxic T lymphocytes, was observed together with adipocyte cell death in human atria. CONCLUSION: Atrial fibrillation is associated with the fibrosis of subepicardial fatty infiltrates, a process in which cytotoxic lymphocytes might be involved. This remodelling of the atrial subepicardium could contribute to structural remodelling forming a substrate for AF.

A Moodle-based blended learning solution for physiology education in Montenegro: a case study.

This study evaluates the impact of web-based blended learning in the physiology course at the Faculty of Medicine, University of Montenegro. The two main goals of the study were: to determine the impact of e-learning on student success in mastering the course, and to assess user satisfaction after the introduction of e-learning. The study compared a group of students who attended the physiology course before, with a group of students who attended the physiology course after the Moodle platform was fully implemented as an educational tool. Formative and summative assessment scores were compared between these two groups. The impact of high vs. low Moodle use on the assessment scores was analyzed. The satisfaction among Moodle users was assessed by the survey. The study found that attendance of face-to-face lectures had a positive impact on academic performance. The introduction of Moodle in the presented model of teaching increased interest of students, attendance of face-to-face lectures, as well as formative and summative scores. High frequency of Moodle use was not always associated with better academic performance, suggesting that the introduction of a new method of teaching was most likely equally accepted by low- and high-achieving students. Most of the students agreed that Moodle was easy to use and it complemented traditional teaching very well, but it could not completely replace traditional face-to-face lectures. The study supports continuing the use of web-based learning in a form of blended learning for physiology, as well as for other courses in medical education.

Clinicopathological characteristics and survival in Serbian patients with renal cell carcinoma: a retrospective analysis.

PURPOSE: Indications of kidney cancer outcome in lowerincome countries are based on an incidence/mortality ratio due to lack of survival information. This study was conducted to provide outcome data in Serbian patients with renal cell carcinoma (RCC) and to identify prognostic factors that could affect their overall survival (OS). METHODS: This retrospective study included 185 patients who underwent nephrectomy. We assessed certain clinicopathological data including age, gender, tumor size, grade, stage and histological subtypes for their possible impact on OS. RESULTS: The 5-year OS was 63.2%. Significant association was found between OS and age (log-rank 12.455, p=0.006), tumor size (log-rank 26.425, p=0.000), grade (log-rank 13.249, p=0.000) and stage (log-rank 43.235, p=0.000). Univariate analysis indicated size (p=0.000), grade (p=0.001) and stage (p=0.000) as prognostic factors for OS. In multivariate analysis, grade (p=0.014) and stage (p=0.000) remained significant predictors of OS. CONCLUSION: Tumor grade and stage were identified as independent prognostic factors of OS survival in Serbian patients with RCC.

Antioxidant Enzymes in Brain Cortex of Rats Exposed to Acute, Chronic and Combined Stress.

The study deals with manganese superoxide dismutase, copper, zinc superoxide dismutase, and catalase activities in brain cortex of Wistar rats exposed to acute stress (immobilization or cold for 2 h), chronic stress (long-term isolation or long-term forced swimming for 21 days), or to combined chronic/acute stress. We observed that i) single episodes of acute stress by immobilization increased activity of both superoxide dismutases; ii) both types of chronic stresses significantly elevated activities of all examined enzymes; iii) chronic social isolation was a much stronger stressor than physical stress by swimming; iv) in animals pre-exposed to chronic isolation, additional stress by immobilization or cold significantly decreased previously elevated activities of all enzymes, while after chronic swimming, acute immobilization lowered only catalase activity. The obtained results indicate that stress conditions most probably altered the cell redox equilibrium, thus influencing the antioxidant response in brain cortex. Further investigation of neuronal prooxidant/antioxidant cellular conditions is needed to improve the prevention and treatment of various stress induced diseases.

Antioxidative enzymes in irradiated rat brain-indicators of different regional radiosensitivity.

PURPOSE: Previously, we examined manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), and catalase (CAT) activities in rat brain irradiated with 2 or 3 Gy of γ-rays. The results indicated that lower MnSOD activity and inducibility found in hippocampus might explain higher radiosensitivity of this brain region. Thus, in this study, we wanted to determine changes of MnSOD, CuZnSOD, and CAT activities after dose of 5 Gy and to find out if differences in MnSOD activity are caused by changes in its expression. METHODS: Heads of 4-day-old female rats were irradiated with γ-rays, using (60)Co. Animals were sacrificed 1/24 h after exposure. Hippocampus and cortex tissues were prepared for enzyme activity measurements and Western blot analysis. RESULTS: One hour after exposure, γ-rays significantly decreased MnSOD activity in both examined brain regions. Twenty-four hours later, MnSOD recovery showed dose and regional dependence. It was weaker at higher doses and in hippocampal region. MnSOD expression changed in the similar manner as MnSOD activity only at lower doses of γ-rays. In both examined brain regions, gamma radiation significantly decreased CuZnSOD activity and did not change activity of CAT. CONCLUSIONS: Our results confirmed that MnSOD plays an important role in different regional radiosensitivity but also showed that depending on dose, radiation affects MnSOD level by utterly different mechanisms. Postradiation changes of CuZnSOD and CAT are not regionally specific and therefore, cannot account for the different radiosensitivity of the hippocampus and cortex.

Antioxidant status in women with uterine leiomyoma: relation with sex hormones.

Uterine leiomyomas are benign soft-tissues tumors that arise from uterine smooth muscle tissue. Etiopathogenesis of leiomyomas is not well understood. We aimed to examine whether antioxidant enzyme activities and lipid hydroperoxides level in patients with leiomyoma are influenced by changes in sex hormones and gonadotropins (estradiol (E2), progesterone, FSH, and LH) during menstrual cycle and in postmenopause. The material consisted of blood and uterine tissue specimens. Hormone concentrations were determined and assays for superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and lipid hydroperoxides concentration were performed. In blood of examined women, a significant difference in catalase, glutathione peroxidase and glutathione reductase activity was recorded among the phases. There was also a positive correlation between the estradiol/progesterone concentration and the catalase activity. Progesterone negatively correlated with lipid hydroperoxides level. In myoma tissue, we recorded a phase-related difference in lipid hydroperoxides level and activities of superoxide dismutase, glutathione peroxidase activities, and glutathione reductase. Negative correlation was observed between FSH and glutathione peroxidase. The results suggest that antioxidant status in patients with uterine leiomyoma is influenced by the changes in sex hormones during the menstrual cycle and in postmenopause, indicating a role of the observed relationship in the leiomyoma etiology.

Regional changes in elastic fiber organization and transforming growth factor ß signaling in aortas from a mouse model of marfan syndrome.

In Marfan Syndrome (MFS), development of thoracic aortic aneurysms (TAAs) is characterized by degeneration of the medial layer of the aorta, including fragmentation and loss of elastic fibers, phenotypic changes in the smooth muscle cells, and an increase in the active form of transforming growth factor-ß (TGFß), which is thought to play a major role in development and progression of the aneurysm. We hypothesized that regional difference in elastic fiber fragmentation contributes to TGFß activation and hence the localization of aneurysm formation. The fibrillin-1-deficient mgR/mgR mouse model of MFS was used to investigate regional changes in elastin fiber fragmentation, TGFß activation and changes in gene expression as compared to wild-type littermates. Knockdown of Smad 2 and Smad 3 with shRNA was used to determine the role of the specific transcription factors in gene regulation in aortic smooth muscle cells. We show increased elastin fiber fragmentation in the regions associated with aneurysm formation and altered TGFß signaling in these regions. Differential effects of Smad 2 and Smad 3 were observed in cultured smooth muscle cells by shRNA-mediated knockdown of expression of these transcription factors. Differential signaling through Smad 2 and Smad 3 in regions of active vascular remodeling likely contribute to aneurysm formation in the mgR/mgR model of MFS. Increased elastin fiber fragmentation in these regions is associated with these changes as compared to other regions of the thoracic aorta and may contribute to the changes in TGFß signaling in these regions.

Long-term outcome in children with infantile spasms treated with vigabatrin: a cohort of 180 patients.

OBJECTIVE: Evaluation of efficacy of vigabatrin as the first drug in infants with previously untreated infantile spasms (IS) and reporting the long-term outcome. METHODS: We analyzed a cohort of 180 infants with infantile spasms treated with vigabatrin as the first drug. Following initial evaluation and a 48-h basal period for counting the spasms, vigabatrin was administered using the same protocol in all. After 14 days all infants were assessed for therapeutic response (primary outcome). Psychomotor development was evaluated by a psychologist and neurologist prior to the initiation of treatment and during the follow-up. Seizure outcomes were followed prospectively, by seizure types and epilepsy syndromes. Long-term (secondary) outcomes included neurologic status, occurrence of late epilepsy, and developmental/cognitive status. RESULTS: Vigabatrin terminated the spasms in 101 patients (56.9%) at a mean period of 5 days. Patients with normal psychomotor development prior to the onset of spasms responded best. After follow-up of 2.4 to 18.9 years (mean 10.64; standard deviation [SD] 4.40), 38.1% of responders, treated with vigabatrin, had severe neurologic dysfunction, 42% had epilepsy, and 42.2% had unfavorable intellectual outcome. The group with symptomatic etiology and abnormal neurologic status at presentation demonstrated a significantly worse prognosis and a more unfavorable outcome than cryptogenic or idiopathic cases (85.1% and 81.6% versus 14.9% and 0%-p = 0.001). Idiopathic patients treated with vigabatrin were all intellectually normal, except the youngest patient who had borderline cognitive function. SIGNIFICANCE: The most important prognostic factors were the underlying etiology and preexisting developmental profile. Long-term outcome in the patients treated with vigabatrin was similar to the outcome in patients treated with adrenocorticotropic hormone (ACTH) or corticosteroids, as reported in earlier studies. The long-term prognosis of idiopathic cases treated with vigabatrin was favorable.

Motivational Factors Influencing the Choice of Medical Studies and Future Career Plans among Montenegrin Students.

Introduction: There is a concerning trend of emigration among highly educated individuals in Montenegro. This includes medical professionals who seek better job opportunities abroad. The aim of the present study was to identify the primary motivational factors driving Montenegrin medical students to pursue a career in medicine, and whether these factors undergo changes over the course of their studies. Methods: A cross-sectional study included 210 medical students in Montenegro, 27.62% were males, and 72.38% were females. The mean age of the students was 21.90 years (SD=3.05) (range 19-39). Their academic motivation was analysed using the Academic Motivation Scale, previously validated in various cultural contexts. Results: The results showed that autonomous motivation levels were higher than controlled motivation levels (p<0.001) among students in Montenegro, which has been previously associated with better learning outcomes. Students with medical doctors among their family members had higher extrinsic motivation related to rewards and punishments (extrinsic motivation with external regulation p=0.018). Amotivation showed a trend of increasing as the students got closer to graduation (p=0.057). Only 8.1% of students planned a career in primary healthcare, and 1% wished to specialize in family medicine. Conclusions: This study's findings, which indicate high levels of autonomous motivation among medical students, are of significant importance. They contribute to a comprehensive understanding of the motivation factors among medical students and young healthcare professionals in Montenegro. Moreover, they provide a basis for the implementation of strategic interventions to retain highly skilled medical professionals within the country's workforce, thereby addressing the concerning trend of emigration among this group.

Treadmill exercise does not change gene expression of adrenal catecholamine biosynthetic enzymes in chronically stressed rats.

Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase) and cyclic adenosine monophosphate response element-binding (CREB) in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT) in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. Also, we examined how additional acute immobilization stress changes the mentioned parameters. Treadmill running did not result in modulation of gene expression of catecholamine synthesizing enzymes and it decreased the level of CREB mRNA in the adrenal medulla of chronically psychosocially stressed adult rats. The potentially negative physiological adaptations after treadmill running were recorded as increased concentrations of catecholamines and decreased morning CORT concentration in the plasma, as well as the adrenal gland hypertrophy of chronically psychosocially stressed rats. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. Treadmill exercise does not change the activity of sympatho-adrenomedullary system of chronically psychosocially stressed rats.

The frequency of poststroke infections and their impact on early stroke outcome.

INTRODUCTION: Poststroke infections are the most common medical complications of stroke and can occur in up to 65% of patients. The aim of this study was to assess the rate of infectious complications during hospitalization of stroke patients and to evaluate the impact of infection in general, including each of the urinary tract infection (UTI), pneumonia, and sepsis, on fatal and poor functional outcome at discharge. METHODS: This retrospective study enrolled patients who have been diagnosed with acute ischemic stroke treated in a 1-year period. Poor functional outcome at discharge was defined as severe invalidity and included patients with modified Rankin Scale score of 3-5. Univariate and multivariate analyses were performed. RESULTS: We analyzed 133 patients with acute ischemic stroke. Poststroke infection occurred in 63 (47.4%) patients. The most common infection was UTI that was present in 27 (20.3%) patients. Multivariate logistic regression analysis after adjustment for confounders demonstrated that poststroke infection was an independent predictor of poor functional outcome (odds ratio [OR] 12.82, 95% confidence interval [CI] 4.09-40.0, P < .001) and death at discharge (OR 14.92, 95% CI 2.97-76.92, P = .001). When analyzing the impact of each infectious complication, multivariate logistic regression showed that UTIs were an independent predictor of poor functional outcome (OR 14.08, 95% CI 3.06-64.84, P = .001) and death (OR 9.81, 95% CI 1.46-65.68, P = .019) at discharge. CONCLUSION: Infection is a frequent poststroke complication and represents an independent predictor of poor functional and fatal early stroke outcome.

Timing Is Important-Management of Metabolic Syndrome According to the Circadian Rhythm.

Physiological processes occur in accordance with a rhythm regulated by the endogenous biological clock. This clock is programmed at the molecular level and synchronized with the daily light-dark cycle, as well as activities such as feeding, exercise, and social interactions. It consists of the core clock genes, Circadian Locomotor Output Cycles Protein Kaput (CLOCK) and Brain and Muscle Arnt-Like protein 1 (BMAL1), and their products, the period (PER) and cryptochrome (CRY) proteins, as well as an interlocked feedback loop which includes reverse-strand avian erythroblastic leukemia (ERBA) oncogene receptors (REV-ERBs) and retinoic acid-related orphan receptors (RORs). These genes are involved in the regulation of metabolic pathways and hormone release. Therefore, circadian rhythm disruption leads to development of metabolic syndrome (MetS). MetS refers to a cluster of risk factors (RFs), which are not only associated with the development of cardiovascular (CV) disease (CVD), but also with increased all-cause mortality. In this review, we consider the importance of the circadian rhythm in the regulation of metabolic processes, the significance of circadian misalignment in the pathogenesis of MetS, and the management of MetS in relation to the cellular molecular clock.

The role of miRNA in colorectal cancer diagnosis: A pilot study.

Despite recent advances in diagnosis and treatment, colorectal cancer (CRC) remains the third most common cancer worldwide, and has both a poor prognosis and a high recurrence rate, thus indicating the need for new, sensitive and specific biomarkers. MicroRNAs (miRNAs/miRs) are important regulators of gene expression, which are involved in numerous biological processes implicated in tumorigenesis. The objective of the present study was to investigate the expression of miRNAs in plasma and tissue samples from patients with CRC, and to examine their potential as CRC biomarkers. Using reverse transcription-quantitative PCR, it was revealed that miR-29a, miR-101, miR-125b, miR-146a and miR-155 were dysregulated in the formalin-fixed paraffin-embedded tissues of patients with CRC, compared with the surrounding healthy tissue, and these miRNAs were associated with several pathological features of the tumor. Bioinformatics analysis of overlapping target genes identified AGE-RAGE signaling as a putative joint regulatory pathway. miR-146a was also upregulated in the plasma of patients with CRC, compared with the healthy control group, and had a fair discriminatory power (area under the curve, 0.7006), with 66.7% sensitivity and 77.8% specificity. To the best of our knowledge, this distinct five-miRNA deregulation pattern in tumor tissue, and upregulation of plasma miR-146a, were shown for the first time in patients with CRC; however, studies on larger patient cohorts are warranted to confirm their potential to be used as CRC diagnostic biomarkers.

Antioxidant protection against curative and palliative doses of ionizing irradiation in human blood decreases with aging.

Reactive oxygen species (ROS) are independently recognized to play a significant role in radiation-induced damage on healthy tissue and in aging process. However, an age-related alteration of antioxidant (AO) system in radiation response in humans is poorly investigated. The aim of this paper was to evaluate the irradiation effects on the activities and expression of AO system in the blood of healthy women during aging. Blood samples were irradiated with curative and palliative doses of 2 Gy or 9 Gy γ-rays. AO capacity for detoxification of O(2)•(-) and H(2)O(2) in response to 2 Gy γ-irradiation decreases in women above 58 years, while in response to 9 Gy shows signs of weakening after 45 years of age. Due to reduction of AO capacity during aging, cytotoxic effects of curative and palliative doses of irradiation, mediated by ROS, may significantly increase in older subjects, while removal of H(2)O(2) excess could reduce them.