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Therapy with mesenchymal stem cells (MSCs) is promising in many diseases. Evaluation of their efficacy depends on adequate follow-up of MSCs after transplantation. Several studies have shown that MSCs can be labeled and subsequently visualized with magnetic nanoparticles (NPs). We investigated the homing of MSCs labeled with magnetic cobalt ferrite NPs in experimentally induced acute kidney injury in mice. To explore the homing of MSCs after systemic infusion into mice, we developed a pre-infusion strategy for optimal tracing and identification of MSCs with polyacrylic acid-coated cobalt ferrite (CoFe$_2$O$_4$) NPs by light and transmission electron microscopy (TEM) in various organs of mice with cisplatin-induced acute kidney injury and control mice. By correlative microscopy, we detected MSCs labeled with NPs in the lungs, spleen, kidney, and intestine of cisplatin-treated mice and in the lungs and spleen of control mice. Our results confirm that labeling MSCs with metal NPs did not affect the ultrastructure of MSCs and their ability to settle in various organs. This study demonstrates the usefulness of cobalt ferrite NPs in ex vivo visualization of MSCs and offers correlative microscopy as a useful method in routine histopathology laboratories for tracing MSCs in paraffin-embedded tissue.

Cisplatin is one of the most widely used chemotherapeutic drugs in the treatment of a wide range of pediatric and adult malignances. However, it has various side effects which limit its use. Cisplatin mouse models are widely used in studies investigating cisplatin therapeutic and toxic effects. However, despite numerous promising results, no significant improvement in treatment outcome has been achieved in humans. There are many drawbacks in the currently used cisplatin protocols in mice. In the paper, the most characterized cisplatin protocols are summarized together with weaknesses that need to be improved in future studies, including hydration and supportive care. As demonstrated, mice respond to cisplatin treatment in similar ways to humans. The paper thus aims to illustrate the complexity of cisplatin side effects (nephrotoxicity, gastrointestinal toxicity, neurotoxicity, ototoxicity and myelotoxicity) and the interconnectedness and interdependence of pathomechanisms among tissues and organs in a dose- and time-dependent manner. The paper offers knowledge that can help design future studies more efficiently and interpret study outcomes more critically. If we want to understand molecular mechanisms and find therapeutic agents that would have a potential benefit in clinics, we need to change our approach and start to treat animals as patients and not as tools.

Cisplatin is an antitumor drug used in the treatment of a wide variety of malignancies. However, its primary dose-limiting side effect is kidney injury, which is a major clinical concern. To help understand mechanisms involved in the development of kidney injury, cisplatin rodent model has been developed. Given the complex pathogenesis of kidney injury, which involves both local events in the kidney and interconnected and interdependent systemic effects in the body, cisplatin rodent model is indispensable in the investigation of underlying mechanisms and potential treatment strategies of both acute and chronic kidney injury. Cisplatin rodent model is well appreciated and widely used model due to its simplicity. It has many similarities to human cisplatin nephrotoxicity, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using cisplatin model. The present paper is aimed at giving a concise insight into the complex characteristics of cisplatin rodent model and heterogeneity of cisplatin dosage regimens as well as outlining factors that can severely influence the outcome of the model and the study. Challenges for future research are also mentioned.

The essential role of the Crem gene in normal sperm development is widely accepted and is confirmed by azoospermia in male mice lacking the Crem gene. The exact number of genes affected by Crem absence is not known, however a large difference has been observed recently between the estimated number of differentially expressed genes found in Crem knock-out (KO) mice compared to the number of gene loci bound by CREM. We therefore re-examined global gene expression in male mice lacking the Crem gene using whole genome transcriptomeanalysis with Affymetrix microarrays and compared the lists of differentially expressed genes from Crem-/- mice to a dataset of genes where binding of CREM was determined by Chip-seq. We determined the global effect ofCREM on spermatogenesis as well as distinguished between primary and secondary effects of the CREM absence. We demonstrated that the absence of Crem deregulates over 4700 genes in KO testis. Among them are 101 genes associated with spermatogenesis 41 of which are bound by CREM and are deregulated in Crem KO testis. Absence of several of these genes in mouse models has proven their importance for normal spermatogenesis and male fertility. Our study showed that the absence of Crem plays a more important role on different aspects of spermatogenesis as estimated previously, with itsimpact ranging from apoptosis induction to deregulation of major circadian clock genes, steroidogenesis and the cell-cell junction dynamics. Several new genes important for normal spermatogenesis and fertility are down-regulated inKO testis and are therefore possible novel targets of CREM.

The experiments on animals still play an important and yet irreplaceable role in the progress of biomedicine. Accordingly, animal protection legislation is based on the premise that, under certain conditions, it is morally acceptable to use animals for scientific purposes. Directive 86/609/EEC adopted in 1986 has started to regulate the legislation on the protection of animals used for scientific purposes in Europe and in Slovenia. In 2010, after a public consultation involving scientific com- munity and animal protectionist associations, the European Parliament released a revised Directive 2010/63/EU on the protection of animals used for scientific purposes. The aim of the paper is to pres- ent contemporary legislation relating to experimental animals and basic ethical principles that are the foundation of responsible use of animals in research as well as of valid science. The society`s attitude to animals varies throughout history, also thanks to animal experimentation which has definitively confirmed that animals are sentient beings that like humans experience pain, suffering, distres or pleasure. In Western developed societies, the number of people defending ani- mal rights and opposing the use of animals in experiments is increasing. Therefore, there is increas- ing effort and financial stimulation for the development and implementation of the methods to re- place animal experimentation in the EU. But as long as this does not occur, the revised legislation requires careful and responsible use of animals in accordance with the legislative and contemporary ethical principles.

The Role, Significance and Applicability of Aberrant Crypt Foci in Clinical Practice

There is a growing support for the concept that reactive oxygen species, which are known to be implicated in a range of diseases, may be important progenitors in carcinogenesis, including colorectal cancer (CRC). CRC is one of the most common cancers worldwide, with the highest incidence rates in western countries. Sporadic human CRC may be attributable to various environmental and lifestyle factors, such as dietary habits, obesity, and physical inactivity. In the last decades, association between oxidative stress and CRC has been intensively studied. Recently, numerous genetic and lifestyle factors that can affect an individual's ability to respond to oxidative stress have been identified. The aim of this paper is to review evidence linking oxidative stress to CRC and to provide essential background information for accurate interpretation of future research on oxidative stress and CRC risk. Brief introduction of different endogenous and exogenous factors that may influence oxidative status and modulate the ability of gut epithelial cells to cope with damaging metabolic challenges is also provided.

Inflammatory bowel disease (IBD) is a complex multifactorial disease of unknown etiology. Thus, dozens of different animal models of IBD have been developed in past decades. Animal models of IBD are valuable and indispensable tools that provide a wide range of options for investigating involvement of various factors into the pathogenesis of IBD and to evaluate different therapeutic options. However, the dextran sulphate sodium (DSS-) induced colitis model has some advantages when compared to other animal models of colitis. It is well appreciated and widely used model of inflammatory bowel disease because of its simplicity. It has many similarities to human IBD, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using DSS model. As demonstrated in the present paper, various factors may affect susceptibility to DSS-induced lesions and modify results.

Physical Activity, Dietary Fat and Colorectal Cancer

ISVU je Informacijski sustav visokih učilišta koji pruža potporu svim procesima koji se odvijaju na visokom učilištu. U sklopu projekta semantički ISVU (SISVU) uveden je semantički opis dijela podataka koje sadrži ISVU - nastavnih programa visokih učilišta, kao i podataka o nastavnicima. U okviru ovog diplomskog rada, potrebno je proučiti znanstvenu literaturu koja se bavi integracijom različitih izvorišta podataka u semantičkom webu. Stečene spoznaje upotrijebiti pri integraciji semantičkih profila visokoškolskih nastavnika, izgrađenih u okviru projekta Semantički ISVU, s drugim dostupnim podacima u semantičkom webu. Potrebno je ispitati mogućnosti inicijalnog automatskog kreiranja semantičkih profila svih izvođača nastave na temelju dostupnih podataka te predložiti i uvesti proširenja postojećeg semantičkog modela. Osmisliti i realizirati način na koji bi izvođači kasnije mogli sami upravljati vlastitim profilima. Izvršiti analizu iskoristivosti tako opisanih profila nastavnika u okviru semantičkog weba, odnosno putem izgrađenog prototipa pokazati vrijednost koju oni donose pri integraciji s drugim izvorima podataka, kao i naprednom pretraživanju.

Background: Aberrant crypt foci (ACF) are the first neoplastic lesions of the colorectum that are seen by the use of a stereomicroscope or high-magnification chromscopic endoscopy. The association of ACF with colorectal carcinoma (CRC) is supported by shared histological features with colonic polyps and adenomas. ACF exhibit many of the molecular and genetic abnormalities that are involved in the patogenetic cascade of CRC development.Regarding histopathology, ACF are classified as hyperplastic and dysplastic. Hyperplastic ACF display characteristics similar to hyperplastic polyps. They are more common in sporadic cases than in familial adenomatous polyposis (FAP) patients, while dysplastic ACF are much more frequent in FAP patients. Dysplastic ACF are generally accepted as precursors to CRC, but the significance ofhyperplastic ACF in tumor progression is less well established.However, ACF provide an opportunity to investigate and characterize the earliest genetic and molecular alterations in CRC development. As high-magnification chromoscopic colon oscopy (HMCC) now allowsdetection and biopsy of ACF in the mucosa of the large bowel, ACF might serve as a valid biomarker of subsequent adenoma and carcinoma formation. Conclusions: The present article describes the characteristics of ACF as well as their role as a potent biomarker of CRC risk in clinical practice by means of high-resolution chromoendoscopy.

Background Colorectal cancer is one of the most frequent cancers in man. Its incidence is increasing in Slovenia as well as in the developing countries. Itis believed that between 60 % and 80 % of colorectal cancer in Western countries is attributable to environmental factors. The evidence that physicalactivity protects against colorectal cancer is convincing, although the evidence is stronger for colon than for rectum. Conclusions The present paper summarizes the main recently published data concerning an association between physical activity and colon cancer risk and presents proposed beneficial mechanisms of exercise involved in the prevention of cancer.