Evaluation of changes in plasma levels of MMP-8, MMP-13, and Thrombospondin 2 in patients with Osgood–Schlatter disease (OSD) Monika Kulesza, Tomasz Guszczyn, Aleksandra Kicman, Rafał Marecki, Michał Stanisław Kicman, et al. Frontiers in Molecular Biosciences, 2025 Introduction Osgood-Schlatter disease (OSD) is characterized by its relatively frequent occurrence and unknown pathomechanism. It mainly affects young athletes. Matrix metalloproteinases (MMPs) may be involved in the pathogenesis, while Thrombospondin 2 is involved in healing process. Purpose of this study was to determine changes in MMP-8, MMP-13 and Thrombospondin 2 levels in patients with OSD compared to control group (CG). Methods The study was conducted on 140 patients with OSD (age range: 11–15), CG consisted of 100 individuals with minor hand injuries (age range: 12–15). Levels of MMPs and Thrombospondin 2 were determined in plasma using an immunoenzymatic method (ELISA). Results Concentrations of MMP-13 (median: 496.5 ng/mL; p < 0.0001) and Thrombospondin 2 (median: 21.05 pg/mL; p < 0.0001) were higher in patients with OSD, while MMP-8 values (median: 26.60 ng/mL; p < 0.001) were lower in patients with OSD compared to CG (58.08 ng/mL; 14.43 pg/mL; 95.91 ng/mL; respectively). Significant correlations were found between the parameters studied, and the highest AUC (area under curve) was obtained for MMP-13 in the OSD group. Discussion The studied compounds have potential as additional tests to distinguish OSD from other diseases, and MMP-13 may be involved in the pathogenesis of OSD.
Diagnostic Utility of Metalloproteinases from Collagenase Group (MMP-1, MMP-8 and MMP-13) in Biochemical Diagnosis of Ovarian Carcinoma Aleksandra Kicman, Ewa Gacuta, Rafał Marecki, Michał Stanisław Kicman, Monika Kulesza, et al. Cancers, 2024 Background: Ovarian carcinoma (OC) has an unfavorable prognosis due to lack of screening and an asymptomatic course. New diagnostic methods are being sought to enable earlier diagnosis of this condition. The purpose of this study was to determine the diagnostic utility of collagenases (MMP-1, MMP-8 and MMP-13) in the diagnosis of OC compared to HE4 and CA125 and the ROMA. Methods: The study group consisted of 120 patients with OC, the control group: 70 patients with benign ovarian lesions (BLs) and 50 healthy women (HS). MMP-1, MMP-8 and MMP-13 were determined by ELISA and HE4 and CA125 by CMIA. Results: OC patients had higher levels of MMP-1 and MMP-13 compared to the BL and HS groups. MMP-1 (SE: 81.66%; SP: 94%; PPV: 97.02%; NPV: 68.11%; AUC: 0.9625) and MMP-13 (SE: 77.50%; SP: 94%; PPV: 96.875%; NPV: 63.51%; AUC: 0.917) showed similar or higher diagnostic values to routine markers (HE4: SE:85%; SP: 92%; PPV: 96.22%; NPV: 71.875%; AUC: 0.943; CA125: SE: 80%; SP: 98%; PPV: 98.96%; NPV: 67.12%; AUC: 0.909) and the ROMA (SE: 90.83%; SP: 94%; PPV: 97.32%; NPV: 81.03%; AUC: 0.955). Performing combined analyses of individual MMPs and MMPs with ROMA was associated with further increases in diagnostic parameters. Conclusions: MMP-1 and MMP-13 have shown preliminary potential as diagnostic markers and auxiliary markers to ROMA in biochemical diagnosis of OC.
Diagnostic Utility of Selected Matrix Metalloproteinases (MMP-2, MMP-3, MMP-11, MMP-26), HE4, CA125 and ROMA Algorithm in Diagnosis of Ovarian Cancer Aleksandra Kicman, Ewa Gacuta, Monika Kulesza, Ewa Grażyna Będkowska, Rafał Marecki, et al. International Journal of Molecular Sciences, 2024 Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm.
Zuranolone – synthetic neurosteroid in treatment of mental disorders: narrative review Rafał Marecki, Joanna Kałuska, Agata Kolanek, Dominika Hakało, Napoleon Waszkiewicz Frontiers in Psychiatry, 2023 With each passing year, the number of people suffering from mental disorders grows at a disturbing speed. Neuroactive steroids are a new promising group of drugs with the potential for use in many diseases like postpartum depression, postnatal psychosis, major depression, insomnia, bipolar disorder, and Parkinson’s tremor, due to their ability to modulate the activity of GABAA receptor. Neurosteroids are progesterone metabolites that are synthesized from cholesterol or steroid hormones in various brain regions. They regulate neuronal development, regeneration, and neurotransmission. They are implicated in mood disorders, anxiety disorders, schizophrenia, PTSD, and impulsive aggression. Neurosteroids have been studied for their potential to prevent or treat neurodegenerative diseases such as Alzheimer’s disease and HIV-associated dementia. They can promote neurogenesis, neuronal survival, myelination, and memory function. They can also affect the growth and sensitivity of hormone-dependent brain tumors such as gliomas. Zuranolone, a newly registered neurosteroid drug has shown huge flexibility in both clinical and ambulatory treatment thanks to its pharmacokinetic traits, especially the possibility for oral administration, unlike its predecessor Brexanolone. Zuranolone is a synthetic positive allosteric modulator of the GABAA receptor that can be taken orally. The review aims to summarize the current knowledge on zuranolone as a novel neurosteroid drug for various mental disorders, especially for postpartum mental disorders for which this drug was meant originally. It covers studies indexed in the PubMed, Scopus, and Web of Science databases published since 2017. Keywords used in the search, as well as inclusion and exclusion criteria, are given in the aims and methodology section. The review explains the evidence for the role of neurosteroids, especially allopregnanolone, in the pathophysiology and treatment of postpartum depression. It discusses the mechanisms of neurosteroid action, the changes in neurosteroid levels during pregnancy and postpartum, and the clinical trials of brexanolone and zuranolone, two synthetic analogs of allopregnanolone, for postpartum depression. It provides an overview of the biosynthesis and metabolism of neurosteroids in the central and peripheral nervous system. Furthermore, it explains the different sources and pathways of neurosteroid production and the factors that influence their synthesis and regulation, such as stress, hormones, drugs, and genetic variations. The review also explores the potential relevance of neurosteroids for other psychiatric disorders, such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD), schizophrenia, and premenstrual dysphoric disorder. Finally, it highlights the associations between neurosteroid levels and symptom severity and the effects of neurosteroid modulation on mood, cognition, and neuroplasticity.
