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.

Neurodegenerative diseases comprise a large number of disorders with high impact on human health. Neurodegenerative processes are caused by various etiological factors and differ in their clinical presentation. Neuroinflammation is widely discussed as both a cause and a consequence in the manifestation of these disorders. The interplay between the two entities is considered as a major contributor to the ongoing disease progression. An attentive search and implementation of new and reliable markers specific for the processes of inflammation and degeneration is still needed. YKL-40 is a secreted glycoprotein produced by activated glial cells during neuroinflammation. Neuron-specific enolase (NSE), expressed mainly by neuronal cells, is a long-standing marker for neuronal damage. The aim of this review is to summarize, clarify, and evaluate the potential significance and relationship between YKL-40 and NSE as biomarkers in the monitoring and prognosis of a set of neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. YKL-40 appears to be a more reliable biomarker in neurological diseases than NSE. The more prominent expression pattern of YKL-40 could be explained with the more obvious involvement of glial cells in pathological processes accompanying each neurodegenerative disease, whereas reduced NSE levels are likely related to low metabolic activity and increased death of neurons.

Almost all transcribed human genes undergo alternative RNA splicing, which increases the diversity of the coding and non-coding cellular landscape. The resultant gene products might have distinctly different and, in some cases, even opposite functions. Therefore, the abnormal regulation of alternative splicing plays a crucial role in malignant transformation, development, and progression, a fact supported by the distinct splicing profiles identified in both healthy and tumor cells. Drug resistance, resulting in treatment failure, still remains a major challenge for current cancer therapy. Furthermore, tumor cells often take advantage of aberrant RNA splicing to overcome the toxicity of the administered chemotherapeutic agents. Thus, deciphering the alternative RNA splicing variants in tumor cells would provide opportunities for designing novel therapeutics combating cancer more efficiently. In the present review, we provide a comprehensive outline of the recent findings in alternative splicing in the most common neoplasms, including lung, breast, prostate, head and neck, glioma, colon, and blood malignancies. Molecular mechanisms developed by cancer cells to promote oncogenesis as well as to evade anticancer drug treatment and the subsequent chemotherapy failure are also discussed. Taken together, these findings offer novel opportunities for future studies and the development of targeted therapy for cancer-specific splicing variants.

The aim of our study was to analyze the level of the glycoprotein YKL-40 in patients with active knee osteoarthritis (OA) and to search possible correlations with local inflammation and ultrasound (US) findings.Material and methods: A prospective study with fifty consecutive patients with active knee OA (diagnosed based on the American College of Rheumatology criteria for OA with radiographic confirmation) was performed. Concentrations of YKL-40 in serum and synovial fluid were measured by ELISA. US examinations – Gray scale (GS) US and Power Doppler (PD) US – of the knee was performed according to international guidelines. The suprapatellar, medial and lateral parapatellar recesses were scanned in each knee to evaluate synovial hypertrophy and vascularization.Results: Forty women (mean age 61.50±11.33 years old) and 10 men (aged 68.50±6.60 years old) were enrolled. We found that the synovial level of the glycoprotein (237.80±104.08 ng/ml) was significantly higher compared to the serum concentration (112.83±60.61 ng/ml, p<0.001). The serum concentration in OA patients was higher comparing with age-matched healthy controls (84.19±11.39 ng/ml) (p<0.05). A statistically significant association between YKL- 40 in synovial fluid and serum levels was shown. We determined a moderately positive linear relationship between the synovial level of the glycoprotein and the serum concentration. No association between the levels of inflammatory markers – erythrocyte sedimentation rate and C-reactive protein – and YKL-40 concentrations was detected. Our study revealed a strong relationship between YKL-40 in synovial fluid and GS US and feeble with PD US. YKL-40 correlated with inflammatory activity in knee joints and neovascularization detected by US.Conclusions: YKL-40 is involved in the pathogenesis of OA synovitis. Evaluation of YKL-40 levels in parallel with US might provide more sensitive and reliable information for the diagnosis and understanding of OA.

Background: Rheumatoid arthritis (RA) causes chronic inflammation and alteration of articular tissue and joints. The pathogenesis of the disease remains unclear although it is known that proinflammatory cytokines play a major role in its induction. YKL-40 is a chitinase-like glycoprotein produced by activated macrophages, neutrophils, arthritic chondrocytes and cancer cells. It has been shown that YKL-40 is implicated in tissue remodeling, angiogenesis and inflammation. Aim: to investigate serum and synovial YKL-40 levels in relation to IL-1β, TNF-α, and IL-6 in RA patients. Materials and methods: Serum and synovial concentrations of YKL-40, TNF-α, IL- 6, and IL-1β were determined by ELISA in 39 patients (mean age 53.18 ± 16.54 yrs) with active RA. Results: Serum YKL-40 levels were increased in all patients. The highest levels were found in synovial fluid (P<0.01). Our study showed a strong association between serum and synovial levels of YKL-40 and serum TNF-α and IL-1 β (P<0.05). Conclusion: This is the first study finding a significant correlation between serum TNF-α and IL-1β and YKL-40 in active RA. We suggest that these molecules together might play a dominant role in the pathogenesis and disease activity and could possibly serve as a new diagnostic constellation in rheumatoid arthritis.

YKL-40 is a heparin- and chitin-binding glycoprotein that belongs to the family of glycosyl hydrolases but lacks enzymatic properties. It affects different (patho)physiological processes, including cancer. In different tumors, YKL-40 gene overexpression has been linked to higher cell proliferation, angiogenesis, and vasculogenic mimicry, migration, and invasion. Because, in colorectal cancer (CRC), the serological YKL-40 level may serve as a risk predictor and prognostic biomarker, we investigated the underlying mechanisms by which it may contribute to tumor progression and the clinical significance of its tissue expression in metastatic CRC. We demonstrated that high-YKL-40-expressing HCT116 and Caco2 cells showed increased motility, invasion, and proliferation. YKL-40 upregulation was associated with EMT signaling activation. In the AOM/DSS mouse model, as well as in tumors and sera from CRC patients, elevated YKL-40 levels correlated with high-grade tumors. In retrospective analyses of six independent cohorts of CRC patients, elevated YKL-40 expression correlated with shorter survival in patients with advanced CRC. Strikingly, high YKL-40 tissue levels showed a predictive value for a better response to cetuximab, even in patients with stage IV CRC and mutant KRAS, and worse sensitivity to oxaliplatin. Taken together, our findings establish that tissue YKL-40 overexpression enhances CRC metastatic potential, highlighting this gene as a novel prognostic candidate, a predictive biomarker for therapy response, and an attractive target for future therapy in CRC.