YKL-40 in health and disease: a challenge for joint inflammation

There is a need of biomarkers to detect early joint inflammation and destruction of cartilage in different types of arthritis. YKL-40, a 39 kD heparin- and chitin-binding secreted glycoprotein (also known as cartilage gp39), was recently discovered. Its exact biological function is still unclear. Specific receptors for YKL-40 have not been identified yet. The clinical significance of YKL-40 as a biomarker is discussed in different aspects. High level of YKL-40 was found in various human diseases associated with inflammatory and neoplastic processes. The review highlights the information available about YKL-40 and its significance in inflammatory joint diseases. We suggest that this glycoprotein might have a promising value as a novel biomarker and could provide additional evidence for inflammation activity in different types of arthritis.Biomedical Reviews 2013, 24: 49-56

YKL‐40: The Search for New Biomarkers in Rheumatoid Arthritis

There is a need for biomarkers to detect early joint inflammation and destruction of cartilage in different types of arthritis. YKL‐40, a 39 kDa heparin‐ and chitin‐binding secreted glycoprotein (also known as human cartilage gp39), has been recently discovered. Its exact biological function is still unclear. Specific receptors for YKL‐40 have not been identified yet. The clinical significance of YKL‐40 as a biomarker is discussed in different aspects. High level of YKL‐40 is found in various human i`nflammatory and neoplastic diseases. We present a review highlighting the information available on YKL‐40 and its significance in inflammatory joint diseases, like rheumatoid arthritis (RA). We also report original personal data on the topic concerning YKL‐40 levels in serum and synovial fluid of patients with RA in comparison with ultrasonographic parameters and cytokine levels. The findings suggest that YKL‐40 might be implicated in the pathogenesis of the disease and could indicate the level of joint inflammation

IMMUNE RESPONSE IN MALIGNANT GLIOMA

Objective: Malignant gliomas are primary brain tumors with excessive mortality and high resistance to chemotherapy and radiotherapy. The survival time for glioblastoma multi­forme is about 6-12 months. As key pathogenetic mechanisms are recognized the massive necrosis, angiogenesis and hypoxia within the tumor, as well as the resistance to apoptosis. It is also suspected that altered immune response might contribute to the fatal clinical outcome.The aim of the present study was to determine the immune status of patients with malignant gliomas.Material and methods: Peripheral blood lymphocytes were collected preoperatively from 9 patients (aged 57-76) diagnosed as anaplastic astrocytoma grade III (n=4) and glioblastoma multiforme (n=5). The following lymphocyte populations were analyzed by flow cytometry: CD19+, CD3+, CD3+CD4+, CD3+CD8+, CD3-CD56+, CD3+CD56+, CD3+CD25+, CD8-CD11b+, CD8+CD11b+, CD8+CD11b-. The results obtained were compared to reference values for each cell population.Results: No significant alterations were detected in CD19+, CD3+, CD3+CD4+, CD3+CD8+ cells, but the CD4/CD8 ratio was below the reference range in some cases. No obvious decrease in (CD3-CD56+) NK cells and (CD3-CD56+) NKT cells was observed in most patients. A reproducible phenomenon of increased CD8+CD11b+ and decreased CD8+CD11b- cells was noticed. These preliminary results suggest that the immune response in patients with malignant glioma is seriously disregulated. The rapid clinical deterioration, relapses and high mortality could be at least partially explained with the suppressed activity of NK-cells which are the major cytotoxic antitumoral cells. The increase in the population of activated suppressor-effector cells also contributes to the unfavourable outcome in malignant brain tumors.Conclusion: This pilot study reveals the presence of altered immune response in malignant gliomas and opens possibilities for prospective investigations concerning immune status and clinical outcome

Expression of histo-blood group antigens in vertebrate gonads

The tissue expression of human histo-blood group antigens (HBGA) in vertebrates, as well as their evolutionary tendencies and relation to histogenesis, especially in the reproductive system, are not entirely understood.The present research comprises a large-scale immunohistochemical study of HBGAA and B expression in ovaries and testicles of 14 species belonging to six classes of free-living vertebrates from Chondrichtyes to Mammalia .We present novel data for ABH antigen reactivity in reproductive organs of vertebrates which have not been studied so far. Our results suggest that HBGA are evolutionary stable structures, most possibly related to vitellogenesis in oocytes with high yolk content. The tendency observed in A and B antigen expression is mostly associated with the processes of gamete differentiation and vitellogenesis, rather than with the evolutionary development of vertebrate species

3D bioprinting as an emerging standard for cancer modeling and drug testing

Neoplastic diseases are a leading cause of death worldwide accounting for 10 million mortalities in 2020. Despite constantly revised and improved therapeutic regimens, the number of fatal cases increases annually. Therefore, better preclinical models are needed to study tumorigenesis and assess new drugs. Although 2D cell cultures significantly contributed to the understanding of tumor biology, they present high clinical trial failure rates. This is because 2D cannot reproduce the intricate tumor architecture and multiple cell interactions. Nevertheless, novel 3D biofabrication technologies and 3D bioprinted tumor models successfully mirror the complexity of human tumors and are currently revolutionizing preclinical cancer research by using live cells encapsulated in a variety of biomaterials. Since bioinks possess excellent chemical and biophysical ECM-like characteristics, this allows for recreation of the intricate tumor-specific architecture with an unmatched level of control, accuracy, and reproducibility. The resulting cellular constructs approximate actual pathological microenvironment of the tumor and some key in vivo processes such as proliferation, differentiation, and metastasis. 3D bioprinted models of glioblastoma, cervical, ovarian, and breast cancer are already being successfully used to study tumorigenesis and cellular response to antitumor drugs. This success showcases the potential of these novel experimental platforms

Neuroinflammation and Autophagy in Parkinson’s Disease—Novel Perspectives

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by the accumulation of α-Synuclein aggregates and the degeneration of dopaminergic neurons in substantia nigra in the midbrain. Although the exact mechanisms of neuronal degeneration in PD remain largely elusive, various pathogenic factors, such as α-Synuclein cytotoxicity, mitochondrial dysfunction, oxidative stress, and pro-inflammatory factors, may significantly impair normal neuronal function and promote apoptosis. In this context, neuroinflammation and autophagy have emerged as crucial processes in PD that contribute to neuronal loss and disease development. They are regulated in a complex interconnected manner involving most of the known PD-associated genes. This review summarizes evidence of the implication of neuroinflammation and autophagy in PD and delineates the role of inflammatory factors and autophagy-related proteins in this complex condition. It also illustrates the particular significance of plasma and serum immune markers in PD and their potential to provide a personalized approach to diagnosis and treatment