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Iron is critically important and highly regulated trace metal in the human body. However, in its free ion form, it is known to be cytotoxic; therefore, it is bound to iron storing protein, ferritin. Ferritin is a key regulator of body iron homeostasis able to form various types of minerals depending on the tissue environment. Each mineral, e.g. magnetite, maghemite, goethite, akaganeite or hematite, present in the ferritin core carry different characteristics possibly affecting cells in the tissue. In specific cases, it can lead to disease development. Widely studied connection with neurodegenerative conditions is widely studied, including Alzheimer disease. Although the exact ferritin structure and its distribution throughout a human body are still not fully known, many studies have attempted to elucidate the mechanisms involved in its regulation and pathogenesis. In this review, we try to summarize the iron uptake into the body. Next, we discuss the known occurrence of ferritin in human tissues. Lastly, we also examine the formation of iron oxides and their involvement in brain functions.

The ependymal lining of the walls of the human brain third ventricle (3v), fourth ventricle (4v) and aqueductus cerebri (A) was studied. For a better localization of different ependymal areas, they were labelled by periventricular structures that represent a basic and stable part of brain nerve tissue and they are localized most closely to ventricle walls. Labelling of individual ependymal areas of the ventricle walls was composed of the number of a brain ventricle, letters: E – ependyma and abbreviation of a Latin name of the periventricular structure, e.g., the corpus mammillare is “CM“. Labelling of ependyma over the corpus mammillare is” 3vE – CM “Results of labelling of ependymal areas were arranged in the form of tables called “ependymal table “(ET), i.e., ET for 3v; ET for 4v; ET for A. It is believed that labelling of individual ependymal areas according to periventricular structures could be useful for unambiguous labelling of ependyma of the ventricle walls and will help to a mutual comparison of the same types of ependymal areas studied by various authors.

Samples taken from the human brain (Globus Pallidus) have been investigated by physical techniques such as light microscopy, scanning electron microscopy, transmission electron microscopy, Mössbauer spectroscopy and SQUID magnetometry. SEM-EDX/TEM investigation reveals multielemental composition of hematite and magnetite nanocrystals with sizes ranging from 40 nm to 100 nm and hematite microcrystals from 3 μm to 7 μm. Room temperature Mössbauer spectra show quadrupole doublets assigning to hematite and ferrihydrite. SQUID measurements of temperature dependence of the mass magnetic susceptibility between T = 2 – 300 K at DC field B 0 = 0.1 T, the field dependence of the mass magnetization taken at the fixed temperature T 0 = 2.0 and 4.6 K and the zero-field cooled and field cooled magnetization experiments (ZFCM/FCM) confirm a presence of ferrimagnetic phases such as maghemite and/or magnetite with hysteresis loops surviving until the room temperature. Differences between these measurements from the point of view of iron oxides detected can indicate important processes in human brain and interactions between ferritin as a physiological source of iron and surrounding environment.

Iron is very important element for functioning of the brain. Its concentration changes with aging the brain or during disease. The aim of our work was the histological examination of content of ferritin and free iron (unbound) in brain cortex in association with Aβ plaques from their earliest stages of accumulation in amyloid plaque forming APP/PS1 transgenic mice. Light microscopy revealed the onset of plaques formation at 8-monthage. Detectable traces of free iron and no ferritin were found around plaques at this age, while the rate of their accumulation in and around Aβ plaques was elevated at 13 months of age. Ferritin accumulated mainly on the edge of Aβ plaques, while the smaller amount of free iron was observed in the plaque-free tissue, as well as in and around Aβ plaques. We conclude that free iron and ferritin accumulation follows the amyloid plaques formation. Quantification of cortical iron and ferritin content can be an important marker in the diagnosis of Alzheimer’s disease.

Osteoarthritis (OA) belongs to chronic degenerative disorders and is often a leading cause of disability in elderly patients. Typically, OA is manifested by articular cartilage erosion, pain, stiffness, and crepitus. Currently, the treatment options are limited, relying mostly on pharmacological therapy, which is often related to numerous complications. The proper management of the disease is challenging because of the poor regenerative capacity of articular cartilage. During the last decade, cell-based approaches such as implantation of autologous chondrocytes or mesenchymal stem cells (MSCs) have shown promising results. However, the mentioned techniques face their hurdles (cell harvesting, low proliferation capacity). The invention of induced pluripotent stem cells (iPSCs) has created new opportunities to increase the efficacy of the cartilage healing process. iPSCs may represent an unlimited source of chondrocytes derived from a patient’s somatic cells, circumventing ethical and immunological issues. Aside from the regenerative potential of iPSCs, stem cell-derived cartilage tissue models could be a useful tool for studying the pathological process of OA. In our recent article, we reviewed the progress in chondrocyte differentiation techniques, disease modeling, and the current status of iPSC-based regenerative therapy of OA.

The human clavicle provides the bony connection between the upper extremity and the axial skeleton and it is reported to be among the first bones ossified and the last bone to fuse. Clavicle development of the studied mammals shows a combination of intramembranous and endochondrial ossification. The covering of its joints in adult humans differs from other joints of long bones. The rat clavicle pattern morphologically appears to be partly different in comparison with the human one. These differences partially restrict the use of the rat as a model for the study of human articular cartilage but on the other hand they can provide some valuable possibilities for application in medical research and practice.

Diabetes type 1 (T1D) is a common autoimmune disease characterized by permanent destruction of the insulin-secreting β-cells in pancreatic islets, resulting in a deficiency of the glucose-lowering hormone insulin and persisting high blood glucose levels. Insulin has to be replaced by regular subcutaneous injections, and blood glucose level must be monitored due to the risk of hyperglycemia. Recently, transplantation of new pancreatic β-cells into T1D patients has come to be considered one of the most potentially effective treatments for this disease. Therefore, much effort has focused on understanding the regulation of β-cells. Induced pluripotent stem cells (iPSCs) represent a valuable source for T1D modelling and cell replacement therapy because of their ability to differentiate into all cell types in vitro. Recent advances in stem cell-based therapy and gene-editing tools have enabled the generation of functionally adult pancreatic β-cells derived from iPSCs. Although animal and human pancreatic development and β-cell physiology have significant differences, animal models represent an important tool in evaluating the therapeutic potential of iPSC-derived β-cells on type 1 diabetes treatment. This review outlines the recent progress in iPSC-derived β-cell differentiation methods, disease modelling, and future perspectives.

Aim Morphological description of milky spots (MSs) in the human greater omentum. Method Samples of the greater omentum collected during surgical procedures were subjected to further histological analysis. Two groups of patients were studied. Group A consisted of patients with colon cancer and peritonitis (stimulated MSs), group B consisted of patients without colon cancer and without peritonitis (unstimulated MSs). In the research, we focused on the cellular composition and differences between stimulated and unstimulated MSs. Results MSs detected in the study were predominantly oval (67 %), round (12 %) or irregular in shape (21 %). The average number of immune cells found in one milky spot (MS) in the group A was 454 (209-694), consisted of T cells in 44.7 % (27-55 %), B cells in 26.8 % (16-34 %), macrophages in 18.3 % (12-27 %) and other immune cells in 10.2 % (6-18 %). The average number of immune cells found in one MS in the group B was 58 (42-100 %), consisted of T cells in 21.1 % (16-22 %), B cells in 18.7 % (13-22 %), macrophages in 46.9 % (33-60 %) and other immune cells in 13.3 % (1-22 %). The average size of MSs in the group A was significantly higher than in the group B: 768 μm (313-1075) to 293 μm (197-421). The results showed that there were significant differences in terms of strong predominance of macrophages in unstimulated milky spots and strong predominance of T cells in stimulated milky spots. Conclusion MSs are specific immune active lymphatic structures on the greater omentum. They play a key role in defense mechanism, especially in peritonitis. Their function is not completely clear in cancer, some authors suggest they might play a significant role in omental metastasis. Further analysing of the morphology and cells interactions of MSs is needed (Tab. 2, Fig. 6, Ref. 20).

Heart failure is the end stage of cardiovascular abnormalities. Studies have primarily focused on the functional changes of cardiomyocytes in the failing heart from different animal models with very little information in the human condition. In addition little is known about the ultrastructural changes that proceed in cardiomyocytes in route to failure. The aim of this study was to examine the ultrastructural changes in the myocardium of human with end-stage heart failure. Left ventricular myocardial tissue samples from 7 patients with end-stage heart failure were examined with transmission and scanning electron microscopy. All heart failure patients were of New York Heart Association (NYHA) class III-IV. The data indicated normal three-dimensional arrangement of cardiac muscle cells in failing myocardium. The various organelles in cardiomyocytes including the nucleus, mitochondria, myofibrils, T-tubules and intercalated discs did not exhibit any remarkable morphological changes. We did observe the appearance of small membrane bound vesicles which appear to be associated with the intercalated discs. The nearly normal ultrastructure and arrangement of cardiomyocytes was remarkable in contrast to the dramatic clinical status of these patients in heart failure. These observations support the hypothesis, that there are no dramatic changes in the ultrastructure or three-dimensional architecture of cardiomyocytes in end-stage failing human myocardium.

Different types of ependymal areas were studied and labelled in the human brain lateral ventricle. Periventricular structures were included in coining the names of the ependymal areas because they represent a basic and stable part of brain nerve structures suitable for the sake of clarity of localization of the ependyma. The labelling of individual ependymal areas was composed from letters: "Lv" (lateral ventricle); "E" (ependymal area) and letters for abbreviations of the closest periventricular structure, e.g. the septum pellucidum is "sp". The labelling for ependymal area over the septum pellucidum is thus "LvE-sp". The studied types of ependymal areas were arranged in so‑called ependymal tables for cornu anterius, pars centralis, cornu inferius and cornu posterius of the human lateral ventricle. Labelling of individual ependymal areas allows for better localization and characterisation of these areas in future studies carried out by various methods (e.g. morphological, biological, molecular) and will prevent from using misnomers with different types of ependymal areas in norm as well as in pathology (Tab. 5, Fig. 6, Ref. 22). Text in PDF www.elis.sk.

Uterine telocytes are interstitial cells characterized by a very long cytoplasmic prolongations, which form a 3D network, functionally integrating a wide variety of different cells. Leiomyomas (uterine fibroids) are benign tumors, which pose a huge threat concerning various health problems in women affected by this condition. The exact cause of leiomyomas development is, however, still largely unknown. Therefore, in an attempt to clarify their etiology, we performed an immunohistochemical characterization of telocytes in leiomyomas as well as in normal myometrium. Tissue samples of intramural leiomyomas from 26 women (age 46.26 ± 11.07) were immunohistochemically stained for the expression of c-kit (CD117) antigen, one of the markers of telocytes. C-kit (CD117) antigen is useful for a routine immunohistochemical identification of uterine telocytes in histological sections of myometrium. In normal, healthy myometrium the c-kit positive telocytes occupy approximately 2.2% of the area of a tissue slide, contrasting with no detectable c-kit positive cells within leiomyomas. As telocytes are thought to be key players in the regulation of tissue homoeostasis, our data suggest that uterine telocyte loss may have important implications in the pathogenesis of leiomyomas. In addition, we supposed to summarize three hypotheses on the association of the cells telocytes loss within the myometrium and formation of leiomyomas. These hypotheses include the loss of telocytes’ functions as “sex hormone sensors” and regulators of smooth muscle cells cycle; the role of telocytes as progenitor cells for the development of leiomyomas; and the hypothesis of decreased angiogenesis after telocytes’ loss with subsequent hypoxia (as a key factor for leiomyomas development).

Knowledge about the three-dimensional fine structure of human heart, as a crucial vital organ of the body, is not only fascinating from the scientific or educational points of view, but has a very important clinical impact. Therefore, we decided to create a three-dimensional atlas of fine structure of the human heart. Tissue samples from ten human hearts were rinsed in phosphate-buffer solution, fixed by glutaraldehyde buffered solution, and post-fixed in osmium tetroxide solution. A gentle dehydration with ethanol in different concentration and drying at the critical point of CO2 were applied as next procedures. Non-conductive specimens were galvanized with thin gold layer and observed in scanning electron microscope. In this study, we present the three-dimensional ultrastructural architecture of the human heart from patients after myocardial infarction, end-stage failing heart as well as without apparent cardiac abnormalities at the time of autopsy. The results are presented as a histological atlas. Its images illustratively describe the fine structure of endocardium including the morphology of Purkyně (Purkinje) fibres, spatial arrangements of cardiac muscle cells inside myocardium or the arrangements of adipose tissue of epicardium. We present also figures of the ultrastructure of papillary muscles, intercalated discs as well as the connective tissue scars after myocardial infarction. The scanning electron microscopy could be a reliable technique to perform a more complete morphological data and to improve our knowledge of some pathological changes of tissues and cells, not always detected by conventional morphological examinations.

Over the last few years, researchers have been studying telocytes, recently described interstitial cells, voraciously. This morphological study focused on the immunohistochemical identification of telocytes and the study of their topographical relations in the wall of the human uterine body and cervix. This study attempted to find the most specific and therefore, the most suitable monoclonal antibody for the study of telocytes via the immunohistochemical methods. Tissue specimens from human uteruses were stained with eight different primary antibodies, to detect the expression of c-kit (CD117), CD34 antigen, vimentin, α-smooth muscle actin, progesterone receptor, desmin, estrogen receptor and S 100 protein. The presence of telocytes was studied in four different histological regions of the uterus: the endometrium and myometrium of the corpus, endocervical mucosa and exocervical mucosa. This study shows that c-kit is the most suitable marker for identification of telocytes in human uterine body and cervix. C-kit positive telocytes within the endometrium, myometrium, as well as the mucosa of the endocervix and exocervix exhibited an assorted variety of shapes from spindle-shaped, triangular to star-shaped. The greatest abundance of c-kit positive telocytes is found within the myometrium. The connective tissue of endocervical mucosa also contains a considerable number of these cells, while the lowest count of c-kit positive telocytes is found within the endometrium and exocervical mucosa.

Human cardiac muscle cells are the most physically energetic cells in the body, and according to various researchers they contain two nuclei in 25240%. In humans, the heart during prenatal development consists mainly of cardiomyocytes with one nucleus. Just before birth, binucleation begins and can extend into early neonatal life. The physiological importance of binucleation is still poorly understood. In this critical review, we provide a summary of the latest research on binucleation of cardiac muscle cells, with special emphasis on the potential application of such knowledge to the fields of regenerative medicine. We summed up and discussed about ten possible biological arguments why binucleation may be beneficial for cardiac muscle cells as well as for the whole myocardium. These arguments include increase of gene expression, purposeful cell shaping, increase of metabolic activity, energysaving growth and function, need for organ growth despite of telomere depletion, adaptation to stress (tissue regeneration), prevention of overgrowth — organ shaping, prevention of aneuploidy, terminally differentiated state (cardiomyocytes exit the cell cycle, end of proliferation activity); or, we hypothesize, binucleation is just an unwanted side product.

Graphical abstract, Bone disorders are a group of varied acute and chronic traumatic, degenerative, malignant or congenital conditions affecting the musculoskeletal system. They are prevalent in society and, with an ageing population, the incidence and impact on the population’s health is growing. Severe persisting pain and limited mobility are the major symptoms of the disorder that impair the quality of life in affected patients. Current therapies only partially treat the disorders, offering management of symptoms, or temporary replacement with inert materials. However, during the last few years, the options for the treatment of bone disorders have greatly expanded, thanks to the advent of regenerative medicine. Skeletal cell-based regeneration medicine offers promising reparative therapies for patients. Mesenchymal stem (stromal) cells from different tissues have been gradually translated into clinical practice; however, there are a number of limitations. The introduction of reprogramming methods and the subsequent production of induced pluripotent stem cells provides a possibility to create human-specific models of bone disorders. Furthermore, human-induced pluripotent stem cell-based autologous transplantation is considered to be future breakthrough in the field of regenerative medicine. The main goal of the present paper is to review recent applications of induced pluripotent stem cells in bone disease modeling and to discuss possible future therapy options. The present article contributes to the dissemination of scientific and pre-clinical results between physicians, mainly orthopedist and thus supports the translation to clinical practice.

The present study deals with histological descriptions of clinically healthy human gingivae through the methods of light, electron microscopy and immunohistochemistry. Even clinically healthy human gingivae are subject to constant bacterial and mechanical influences present in the oral cavity; therefore, the term “normal gingiva” is misleading. The aim of this study was to identify, in clinically healthy gingiva, all active cells through immunohistochemical markers and light and electron microscope examination. In tissue samples from clinically healthy gingivae of nine patients, we observed the presence of different cells (e.g., T- and B-lymphocytes, macrophages, Merkel cells, Langerhans cells, proliferating cells) and some components of their extracellular matrix that use antibodies against S-100 protein, CD68, CD20, CD45RO, CD20, and Ki67. The presence of immunologically active cells and the ultrastructural characteristics of gingivae were also confirmed. The stratified squamous epithelium of human gingiva contains a population of Langerhans cells and intraepithelial T-lymphocytes. The underlying dense connective tissue contains primarily fibroblasts, but also T-lymphocytes, occasionally B-lymphocytes, plasma cells, and macrophages can be seen. As a border between the oral cavity and the internal environment of the human body, the gingivae are an important part of the immune system. Such findings show that, in healthy gingival tissue, there are constantly ongoing anti-inflammatory, immunological, and regenerative reactions and processes.

Nowadays, breast cancer is the leading oncological diagnosis in women worldwide. On the other hand, breast cancer treatment can be considered one of the most progressive therapeutic approach in the medical field of oncology. The invasive types of breast cancer have a tendency to spread via lymphatic route, what brings in the issue of sentinel lymph node - the first node into which the lymph drains from a given anatomical location. This review paper discusses the historical background of the concept of sentinel lymph node and focuses on clinical significance of the positivity of sentinel lymph node(s) as well. Modern-day conservative therapeutic surgery of breast cancer should be in accordance with diagnostic and preventive interventions in the axilla, whose rate of invasiveness and morbidity must be also attenuated without worsening the patient´s prognosis and survival rate. Formerly, a complete axillary lymph node dissection was routinely performed for prophylactic and cancer staging purposes. The indiscriminate application of this approach was replaced by sentinel lymph node biopsy. Along with common histopathological examination, immunohistochemistry, as well as modern techniques of molecular biology are often employed. These state-of-the-art methods enabled the identification of micrometastases, or even nanometastases, though their real prognostic value is yet to be concluded (Ref. 52). Keywords: sentinel node, breast cancer, biopsy, historical background.

The race to make the dream of artificial intelligence a reality comes parallel with the increasing struggle of health care systems to cope with information overload and translational pressure. It is clear that a shift in the way data is generated requires a shift in the way they are processed. This is where AI comes with great promises to solve the problem of volume versus applicability of information in science. In medicine, AI is showing exponential progress in the fields of predictive analysis and image recognition. These promises however, come with an intricate package of ethico-social, scientific and economic implications, towards which a reductionist approach leads to distorted and dramatic predictions. All this, in a time when the growing pressure on healthcare systems towards defensive medicine begs the question of the true need for AI for good medical practice.This article examines the concept and achievements of AI and attempts to offer a complex view on the realistic expectations from it in medicine, in the context of current practice (Ref. 38). Keywords: algorithms, artificial intelligence, image recognition, neural networks, predictive analysis.

A novel approach for stem cell generation is the attempt to induce conversion of the adult somatic cells into pluripotent stem cells so called induced pluripotent stem cells (iPSCs) by introducing specific transcription factors. iPSCs have two essential cell characteristics, they are pluripotent and posses long term cell-renewal capacity. Additionally, iPSCs can be derived from patient-specific somatic cells, thus bypassing ethical and immunological issues. The aim of our study was to reprogram long-term cryopreserved human neonatal fibroblasts by new method using lipid nano-particle technology (Lipofectamine 3000 reagent transfection system) in combination with Epi 5 reprogramming vectors. Obtained iPSCs were characterized by several sophisticated methods of molecular biology and microscopy. Distinct colonies of iPSCs started to appear by day 20 after reprogramming. The presence of iPSCs colonies was proved by alkaline phosphatase (AP) live staining. After manual picking the colonies and their subsequent passaging, they did not lose ability to form embryoid bodies, they were positive for AP, Tra-1-60, and SSEA-5. Moreover, obtained iPSCs expressed pluripotency markers Oct4, Sox2 and Nanog, and the expression levels of chondrogenic, osteogenic and adipogenic markers were significantly higher in comparison to control (p

The lack of effective therapies for different neurodegenerative disorders has placed huge burdens on society. To overcome the restricted capacity of the central nervous system for regeneration, the promising alternative would be to use stem cells for more effective treatment of chronic degenerative and inflammatory neurological conditions and also of acute neuronal damage and from injuries or cerebrovascular diseases. The generation of induced pluripotent stem cells from somatic cells by the ectopic expression of specific transcription factors has provided the regenerative medicine field with a new tool for investigating and treating neurodegenerative diseases, including Alzheimer’s disease (AD). This technology provides an alternative to traditional approaches, such as nuclear transfer and somatic cell fusion using embryonic stem cells. However, due to a problem in standardization of certain reprogramming techniques and systems research, the induced pluripotent stem cell-based technology is still in its infancy. The present paper is aimed at a brief review of the current status in modeling and cell-based therapies for AD.

Unexpected toxicity in areas such as cardiotoxicity, hepatotoxicity, and neurotoxicity is a serious complication of clinical therapy and one of the key causes for failure of promising drug candidates in development. Animal studies have been widely used for toxicology research to provide preclinical security evaluation of various therapeutic agents under development. Species differences in drug penetration of the blood–brain barrier, drug metabolism, and related toxicity contribute to failure of drug trials from animal models to human. The existing system for drug discovery has relied on immortalized cell lines, animal models of human disease, and clinical trials in humans. Moreover, drug candidates that are passed as being safe in the preclinical stage often show toxic effects during the clinical stage. Only around 16% drugs are approved for human use. Research on induced pluripotent stem cells (iPSCs) promises to enhance drug discovery and development by providing simple, reproducible, and economically effective tools for drug toxicity screening under development and, on the other hand, for studying the disease mechanism and pathways. In this review, we provide an overview of basic information about iPSCs, and discuss efforts aimed at the use of iPSC-derived hepatocytes, cardiomyocytes, and neural cells in drug discovery and toxicity testing.

The proliferative activity of tumour cells represents an important prognostic marker in the diagnosis of cancer. One of the methods for assessing the proliferative activity of cells is the immunohistochemical detection of cell cycle-specific antigens. For example, Ki67, proliferating cell nuclear antigen (PCNA), and minichromosome maintenance (MCM) proteins are standard markers of proliferation that are commonly used to assess the growth fraction of a cell population. The function of Ki67, the widely used marker of proliferation, still remains unclear. In contrast, PCNA and MCM proteins have been identified as important participants of DNA replication. All three proteins only manifest their expression during the cell division of normal and neoplastic cells. Since the expression of these proliferative markers was confirmed in several malignant tumours, their prognostic and predictive values have been evaluated to determine their significance in the diagnosis of cancer. This review offers insight into the discovery of the abovementioned proteins, as well as their current molecular and biological importance. In addition, the functions and properties of all three proteins and their use as markers of proliferation in the diagnosis of breast cancer are described. This work also reveals new findings about the role of Ki67 during the mitotic phase of the cell cycle. Finally, information is provided about the advantages and disadvantages of using all three antigens in the diagnosis of cancer.

Human Merkel cells (MCs) were first described by Friedrich S. Merkel in 1875 and named “Tastzellen” (touch cells). Merkel cells are primarily localized in the basal layer of the epidermis and concentrated in touch-sensitive areas. In our previous work, we reported on the distribution of MCs in the human esophagus, so therefore we chose other parts of the human body to study them. We selected the human vagina, because it has a similar epithelium as the esophagus and plays very important roles in reproduction and sexual pleasure. Due to the fact that there are very few research studies focusing on the innervation of this region, we decided to investigate the occurrence of MCs in the anterior wall of the vagina. The aim of our research was to identify MCs in the stratified squamous non-keratinized epithelium of the human vagina in 20 patients. For the identification of Merkel cells by light microscopy, we used antibodies against simple-epithelial cytokeratins (especially anti-cytokeratin 20). We also tried to identify them using transmission electron microscopy. Our investigation confirmed that 10 (50 %) of 20 patients had increased number of predominantly intraepithelial CK20 positive “Merkel-like” cells (MLCs) in the human vaginal epithelium. Subepithelial CK20 positive MLCs were observed in only one patient (5%). We tried to identify them also using transmission electron microscopy. Our investigation detected some unique cells that may be MCs. The purpose of vaginal innervation is still unclear. There are no data available concerning the distribution of MCs in the human vagina, so it would be interesting to study the role of MCs in the vaginal epithelium, in the context of innervation and epithelial biology.

The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential.

BACKGROUND Mobile phone application may cause structural, functional changes and accumulation of toxic elements in brain. OBJECTIVES The aim of this study was to investigate iron accumulation in rabbit cerebellum after exposure to RF EMF with light and scanning electron microscopy. MATERIALS AND METHODS Histochemical analysis of iron distribution by light and electron microscopy with energy-dispersive microanalysis was used. RESULTS Light microscopy revealed dystrophic changes of Purkinje cells in irradiated groups and iron deposits located in various parts of cerebellum. Deposits consists of C, O, Na, Mg, Al, Si, P, S, Cl, Ca and Fe. CONCLUSION Our experiment revealed structural changes of Purkinje cells and iron and aluminium accumulations in stratum granulosum of rabbit's cerebellum after exposure to RF EMF (Fig. 6, Ref. 33).

Acellular dermal matrix (ADM) is a tissue graft of allogeneic origin from post-mortem tissue donors prepared by an innovative decellularization process. The newly developed non-toxic and low cost decellularization process of cadaver origin dermis included ADM in breast reconstruction procedures proved to help coverage of the lower-pole of breast expanders or implants. As the results have shown, it did help to eliminate autologous dermis donor site morbidity along with shortening the operation time by avoiding elevation of additional muscle or fascia during the operation. Main aims of this article include histology evaluation of allogeneic acellular dermal matrix prepared by a new decellularization method and presentation of clinical results of its use. A total of 22 patients underwent 26 ADM based breast reconstructions. The mean patient’s follow up was 12.6 months. Average total size of ADM used for one breast was 273 cm2. Post-operative complications occurred in 3 patients including one expander infection, one expander extrusion and one expander pocket disfiguration. Microscopic analysis of tissue samples has confirmed incorporation of the acellular dermal matrices into the surrounding connective tissue without any noticeable immune reaction. In a majority of the ADM samples we found pseudocapsullar formation on implant side of samples without acute or chronic inflammatory cells. The use of ADM prepared by new preparation method in expansive post mastectomy breast reconstruction was associated by a relatively low complication rate resulting in good outcomes.

Hassall's corpuscles are the most prominent structures in the human thymus. However, relatively few analyses have been performed to determine their function and cellular origins during development. In this study, we evaluated the cellular microenvironment of human thymic Hassall's corpuscles using histochemistry, immunohistochemistry, and transmission electron microscopy. We examined 95 human thymic tissue samples, which were perioperatively obtained from children undergoing cardiac surgery. To characterize the complex cellular microenvironment of human thymic corpuscles, we used a panel of 14 different antibodies to identify discrete cell types. We also utilized various histochemical methods (PAS reaction, alcian blue staining, alkaline phosphatase and acid phosphatase activity staining, von Kossa staining of calcified particles) and transmission electron microscopy to visualize these structures. Considerable variation in the sizes, shapes, and numbers of Hassall's corpuscles was observed, even amongst children of the same age. Inside the largest Hassall's corpuscles, cystic dilatation with an accumulation of cellular debris was found. These morphological observations might be associated with disruptions in the formation, migration, or differentiation of cardiac neural crest cells, which are essential for heart and thymus development. Immunohistochemical staining and electron microscopy revealed that Hassall's corpuscles resemble other types of stratified squamous epithelia. Most Hassall's corpuscles are heterocellular, consisting of thymic epithelial cells, macrophages, interdigitating dendritic cells, myoid cells, and, occasionally, mast cells and lymphocytes. To explore the potential functions of Hassall's corpuscles, we found that the concentrations of B-lymphocytes and BCL2-positive lymphocytes suggested a role in regulation of lymphopoiesis. We also found that these structures do not originate from the perivascular epithelium as previously proposed, nor could we identify blood or lymph endothelial cells in close proximity. This leaves the origins of Hassall's corpuscles an open question.

Key morphological discoveries in recent years have included the discovery of new cell populations inside the heart called cardiac telocytes. These newly described cells of the connective tissue have extremely long cytoplasmic processes through which they form functionally connected three-dimensional networks that connect cells of the immune system, nerve fibers, cardiac stem cells, and cardiac muscle cells. Based on their functions, telocytes are also referred to as “connecting cells” or “nurse cells” for cardiac progenitor stem cells. In this critical review, we provide a summary of the latest research on cardiac telocytes localized in all layers of the heart — from the historical background of their discovery, through ultrastructural, immunohistochemical, and functional characterizations, to the application of this knowledge to the fields of cardiology, stem cell research, and regenerative medicine.

Introduccion. El objetivo principal de nuestro trabajo es el estudio histologico del desarrollo del timo humano entre la 5a y la 8a semana de gestacion. Describimos varios terminos embriologicos poco usados como: timo secundus , descensus thymi (la base embriologica para situar el timo en la garganta), ductus timicus (la base embriologica para el defecto innato llamado conducto timofaringeo con posibilidad de formar un quiste). Material y metodo. Nuestras observaciones se basan en la investigacion de 18 embriones humanos entre la 6a y la 8a semana de gestacion. Resultados. La base del timo es comun con la base de las glandulas paratiroideas. Es comparable con las bolsas faringeas ( saccus pharyngeus ) en los embriones largos de 8 a 9 mm. La proliferacion endodermal del epitelio en el tercer foco faringeo ( focus faringeus 3 ) es muy visible. La parte craneal y la parte dorsal son la base de origen de las glandulas paratiroideas inferiores. La parte caudal y la parte ventral son la base para el timo. Hemos observado tambien la notable proliferacion del epitelio en la segunda bolsa faringea, llamado por algunos autores Timo secundus . En nuestra opinion, en el ser humano no se forma un timo funcional en este lugar y la proliferacion del epitelio en la mayoria de los casos, se detiene pronto. Conclusion. En este trabajo ofrecemos una vista general sobre la importancia clinica del desarrollo del timo y la descripcion de los defectos innatos mas frecuentes del mismo. Introduction. The aim of our morphological study is to describe the development of human thymus from 5 th up to 8 th week after fertilization in the context of its phylogenesis. We explicate some of the “forgotten” embryological terms with respect to their functions in thymic development, such as “ thymus secundus ”, “ descensus thymi ” (an embryological basis for cervical thymus) and “ ductus thymicus ” (an embryologic basis for a congenital anomaly called thymopharyngeal duct with possible thymic cyst). Material and methods. Our findings are based on the study of 18 human embryos from 6 th to 8 th week of development. Results. The first primordia of the thymus and parathyroid glands within the endoderm of pharyngeal pouches can be seen in 8 to 9 mm crown-to-rump-length stages. The most evident epithelial proliferation is visible in the paired third pharyngeal pouch ( saccus pharyngeus tertius ): the cranial dorsal part of pharyngeal pouch initiates the inferior parathyroid gland and the caudal ventral part of the pouch gives rise to the epithelial thymus. We found an obvious endodermal epithelial proliferation also in the second pharyngeal pouch. Some authors depict this proliferation as “ thymus secundus ”, but the proliferation of endoderm close down and the functional second thymus does not develop in human embryos. Conclusion. In our work we also review the clinical significance of early thymus development, as well as the most common developmental anomalies of thymus.

Neurodegenerative disorders include a variety of hereditary or sporadic diseases involving the chronic, progressive loss on neural tissue. Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting more than 6 million people worldwide (Wan et al., 2015). Degeneration of nigrostriatal dopamine (DA) neurons is the main pathology in PD, although other dopaminergic and non-dopaminergic systems are also affected. Characteristic symptoms are rigidity, hypokinesia, tremor, and postural instability. The loss of DA neurons is accompanied by lewy bodies and lewy neuritis, which are mainly formed by insoluble aggregates of alpha-synuclein and Tau protein and might restrain the survival and development of newborn neurons. Etiology of PD remains unclear, however interactions between environmental and genetic factors are believed to cause the loss of nigral DA neurons and ensuing locomotor system. Research indicated that increasing level of iron, oxidative stress, mitochondrial and ubiquitin-proteasome system dysfunction, inflammation, and apoptosis may lead to the progression of PD (Pu et al., 2012; Zhu et al., 2016).