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Article: Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma.

Niemira, Magdalena / Bielska, Agnieszka / Chwialkowska, Karolina / Raczkowska, Justyna / Skwarska, Anna / Erol, Anna / Zeller, Anna / Sokolowska, Gabriela / Toczydlowski, Damian / Sidorkiewicz, Iwona / Mariak, Zenon / Reszec, Joanna / Lyson, Tomasz / Moniuszko, Marcin / Kretowski, Adam

Frontiers in molecular biosciences

2024 Volume 11, Page(s) 1368372

Abstract: According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision ... ...

Abstract	According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2-3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications.
Language	English
Publishing date	2024-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2024.1368372
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Article ; Online: Combinatory Treatment with miR-7-5p and Drug-Loaded Cubosomes Effectively Impairs Cancer Cells.

Gajda, Ewa / Godlewska, Marlena / Mariak, Zenon / Nazaruk, Ewa / Gawel, Damian

International journal of molecular sciences

2020 Volume 21, Issue 14

Abstract: Background: Multidrug resistance (MDR) is an emerging problem in the treatment of cancer. Therefore, there is a necessity for novel strategies that would sensitize tumor cells to the administered chemotherapeutics. One of the innovative approaches in ... ...

Abstract	Background: Multidrug resistance (MDR) is an emerging problem in the treatment of cancer. Therefore, there is a necessity for novel strategies that would sensitize tumor cells to the administered chemotherapeutics. One of the innovative approaches in fighting drug-resistant tumors is the treatment of cancer with microRNA (miRNA), or the use of cubosomes (lipid nanoparticles) loaded with drugs. Here, we present a study on a novel approach, which combines both tools. Methods: Cubosomes loaded with miR-7-5p and chemotherapeutics were developed. The effects of drug- and miRNA-loaded vehicles on glioma- (A172, T98G), papillary thyroid- (TPC-1) and cervical carcinoma-derived (HeLa) cells were analyzed using molecular biology techniques, including quantitative real-time PCR, MTS-based cell proliferation test, flow cytometry and spheroids formation assay. Results: The obtained data indicate that miR-7-5p increases the sensitivity of the tested cells to the drug, and that nanoparticles loaded with both miRNA and the drug produce a greater anti-tumor effect in comparison to the free drug treatment. It was found that an increased level of apoptosis in the drug/miRNA co-treated cells is accompanied by an alternation in the expression of the genes encoding for key MDR proteins of the ABC family. Conclusions: Overall, co-administration of miR-7-5p with a chemotherapeutic can be considered a promising strategy, leading to reduced MDR and the induction of apoptosis in cancer cells.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Line, Tumor ; Drug Carriers/chemistry ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic/drug effects ; HeLa Cells ; Humans ; MicroRNAs/administration & dosage ; MicroRNAs/genetics ; MicroRNAs/pharmacology ; Neoplasms/genetics ; Neoplasms/therapy
Chemical Substances	Antineoplastic Agents ; Drug Carriers ; MIRN7 microRNA, human ; MicroRNAs
Language	English
Publishing date	2020-07-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21145039
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Article: Change in Blood Flow Velocity Pulse Waveform during Plateau Waves of Intracranial Pressure.

Sawicki, Karol / Placek, Michał M / Łysoń, Tomasz / Mariak, Zenon / Chrzanowski, Robert / Czosnyka, Marek

Brain sciences

2021 Volume 11, Issue 8

Abstract: A reliable method for non-invasive detection of dangerous intracranial pressure (ICP) elevations is still unavailable. In this preliminary study, we investigate quantitatively our observation that superimposing waveforms of transcranial Doppler blood ... ...

Abstract	A reliable method for non-invasive detection of dangerous intracranial pressure (ICP) elevations is still unavailable. In this preliminary study, we investigate quantitatively our observation that superimposing waveforms of transcranial Doppler blood flow velocity (FV) and arterial blood pressure (ABP) may help in non-invasive identification of ICP plateau waves. Recordings of FV, ABP and ICP in 160 patients with severe head injury (treated in the Neurocritical Care Unit at Addenbrookes Hospital, Cambridge, UK) were reviewed retrospectively. From that cohort, we identified 18 plateau waves registered in eight patients. A "measure of dissimilarity" (Dissimilarity/Difference Index, DI) between ABP and FV waveforms was calculated in three following steps: 1. fragmentation of ABP and FV signal according to cardiac cycle; 2. obtaining the normalised representative ABP and FV cycles; and finally; 3. assessing their difference, represented by the area between both curves. DI appeared to discriminate ICP plateau waves from baseline episodes slightly better than conventional pulsatility index did: area under ROC curve 0.92 vs. 0.90, sensitivity 0.81 vs. 0.69, accuracy 0.88 vs. 0.84, respectively. The concept of DI, if further tested and improved, might be used for non-invasive detection of ICP plateau waves.
Language	English
Publishing date	2021-07-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci11081000
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Article ; Online: Endoscopic transconjunctival optic nerve sheath fenestration for progressive idiopathic visual field deficit: a case report.

Lyson, Tomasz / Sieskiewicz, Andrzej / Chrzanowski, Robert / Konopinska, Joanna / Rogowski, Marek / Mariak, Zenon

The Journal of international medical research

2021 Volume 49, Issue 10, Page(s) 3000605211048362

Abstract: Intra-orbital optic nerve sheath fenestration (ONSF) is an effective option in patients with progressive vision loss due to idiopathic intracranial hypertension. Most proposed techniques involve surgical trauma and require disinsertion of the medial ... ...

Abstract	Intra-orbital optic nerve sheath fenestration (ONSF) is an effective option in patients with progressive vision loss due to idiopathic intracranial hypertension. Most proposed techniques involve surgical trauma and require disinsertion of the medial rectus muscle; thus, less invasive surgical procedures are needed. Here, a feasible and effective technique of endoscopic intra-orbital ONSF through a conjunctival incision is presented, in a patient with a progressively compromised visual field, papilloedema, and distended subarachnoid space around the optic nerves. The retrobulbar segment of the optic nerve was exposed for incision, avoiding manipulation of the lateral orbital rim bones and irritation of the ciliary microvessels and nerves. The patient regained the entire visual field. ONSF was safely and effectively performed endoscopically through a narrow corridor gained by brushing away the orbital fat with minimal traction on the medial rectus muscle. The small postoperative wound was associated with faster and easier convalescence, and less tissue trauma versus conventional open approaches.
MeSH term(s)	Humans ; Optic Nerve/diagnostic imaging ; Optic Nerve/surgery ; Papilledema ; Pseudotumor Cerebri ; Vision Disorders ; Visual Fields
Language	English
Publishing date	2021-10-25
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	184023-x
ISSN	1473-2300 ; 0300-0605 ; 0142-2596
ISSN (online)	1473-2300
ISSN	0300-0605 ; 0142-2596
DOI	10.1177/03000605211048362
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Article ; Online: Plasma concentration of Bisphenol A and leptin in patients with meningioma and glioma: A pilot study.

Komarowska, Marta / Chrzanowski, Robert / Tylicka, Marzena / Rutkowski, Robert / Mariak, Zenon / Zelazowska-Rutkowska, Beata / Lyson, Tomasz / Hermanowicz, Adam

Advances in medical sciences

2022 Volume 67, Issue 2, Page(s) 229–233

Abstract: Purpose: Recent increase in incidence of meningiomas suggests the need to search for new risk factors. Leptin, a potentially pro-angiogenic and proliferative agent, could be a candidate for this role, as its expression correlates with body mass index ( ... ...

Abstract	Purpose: Recent increase in incidence of meningiomas suggests the need to search for new risk factors. Leptin, a potentially pro-angiogenic and proliferative agent, could be a candidate for this role, as its expression correlates with body mass index (BMI). Because development of meningioma has also been linked to sex hormones, bisphenol A (BPA), a known xenoestrogen, can also be taken into consideration as a potential risk factor. The aim of this study was to determine plasma concentrations of both substances in patients with meningiomas and to match it to patients with gliomas - a group of brain tumors less hormone- and BMI-dependent. Materials & methods: Concentrations of BPA and leptin were measured in plasma of 24 patients with low grade meningioma and in 29 patients with glioma, using gas chromatography-mass spectrometry (GC-MS) and ELISA kits, respectively. The concentrations of both substances in patients with neoplasms were interpreted in relation to their concentration in healthy population, published in recent reports. Results: Free and conjugated BPA were present in both meningioma and glioma patients. Moreover, their concentrations far exceeded those reported in the healthy population. Nevertheless, the level of leptin revealed to be significantly higher in meningioma patients than in glioma patients. Conclusions: Occurrence of both meningioma and glioma may be accompanied by increased concentrations of leptin and BPA. Further large-scale studies are needed to clarify whether the presence of both substances may play a role in pathogenesis or influence clinical course in patients with brain neoplasms.
MeSH term(s)	Humans ; Meningioma/etiology ; Meningioma/pathology ; Pilot Projects ; Leptin ; Glioma/etiology ; Glioma/pathology ; Brain Neoplasms/pathology ; Gonadal Steroid Hormones ; Meningeal Neoplasms/complications ; Meningeal Neoplasms/pathology
Chemical Substances	bisphenol A (MLT3645I99) ; Leptin ; Gonadal Steroid Hormones
Language	English
Publishing date	2022-05-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2273668-2
ISSN	1898-4002 ; 1896-1126
ISSN (online)	1898-4002
ISSN	1896-1126
DOI	10.1016/j.advms.2022.04.002
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Article ; Online: Canonical NF-κB signaling pathway and GRO-α/CXCR2 axis are activated in unruptured intracranial aneurysm patients.

Kamińska, Joanna / Tylicka, Marzena / Dymicka-Piekarska, Violetta / Mariak, Zenon / Matowicka-Karna, Joanna / Koper-Lenkiewicz, Olga Martyna

Scientific reports

2022 Volume 12, Issue 1, Page(s) 21375

Abstract: Activation of the nuclear factor kappa-B (NF-κB) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-κB p65 subunit and the GRO-α chemokine and its receptor ... ...

Abstract	Activation of the nuclear factor kappa-B (NF-κB) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-κB p65 subunit and the GRO-α chemokine and its receptor CXCR2 concentrations in unruptured intracranial aneurysm patients (UIA, n = 25) compared to individuals without vascular changes in the brain (n = 10). It was also analyzed whether tested proteins are related to the size and number of aneurysms. Cerebrospinal fluid (CSF) and serum protein levels were measured using the ELISA method. Median CSF and serum NF-κB p65 concentrations were significantly lower, while median CSF GRO-α and CXCR2 concentrations were significantly higher in UIA patients compared to the control group. CSF and serum NF-κB p65 concentrations negatively correlated with the number of aneurysms. In UIA patients the median GRO-α concentration was two-fold and CXCR2 almost four-fold higher in CSF compared to the serum value. CSF GRO-α concentration positively correlated with the size of aneurysms.Significantly decreased CSF NF-κB p65 and significantly increased CSF GRO-α and its CXCR2 receptor concentrations in UIA patients compared to the control group may altogether suggest that the canonical NF-κB signaling pathway is activated and its target pro-inflammatory genes are highly expressed in UIA patients. However, to unequivocally assess the involvement of the classical NF-κB pathway with the participation of the NF-κB p65 subunit and the GRO-α/CXCR2 axis in the formation of IA, further in vivo model studies are needed.
Language	English
Publishing date	2022-12-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-25855-2
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Article: Biomechanical evaluation of single- and multi-level anterior cervical discectomy and fusion with polyetheretherketone cages: radiological and clinical outcomes.

Zapolska, Gabriela / Kwiatkowski, Michał / Turek, Grzegorz / Mariak, Zenon / Hermanowicz, Adam

Neurologia i neurochirurgia polska

2019 Volume 53, Issue 5, Page(s) 358–362

Abstract: Objective: The aim of this study was to analyse the outcomes of single- and multi-level anterior cervical discectomy and fusion (ACDF) with standalone polyetheretherketone (PEEK) cages, with particular emphasis on the risk of secondary adjacent segment ... ...

Abstract	Objective: The aim of this study was to analyse the outcomes of single- and multi-level anterior cervical discectomy and fusion (ACDF) with standalone polyetheretherketone (PEEK) cages, with particular emphasis on the risk of secondary adjacent segment disease. Materials and methods: This retrospective study included 30 patients with single- or multi-level cervical disc herniation. Before the ACDF, and one year thereafter, the patients underwent clinical and radiological evaluation including determination of cervical pain severity with a numerical rating scale (NRS), and a survey with a Polish adaptation of the neck disability index questionnaire (NDI-PL). Biomechanical parameters of the cervical spine were determined using the Cobb method. Results: One year after ACDF, all patients had achieved complete fusions, and 97% showed a significant reduction of pain severity. Also, a significant decrease in all NDI-PL indices was observed. A significant decrease in overall cervical spine mobility coexisted with a significant increase in the mobility of the segment above the one operated upon and a non-significant decrease in the mobility of the segment below. No statistically significant change was found in the intervertebral disc space height (IVH) above and below the operated segment, and no evidence of degeneration within the segments adjacent to the operated one was documented. Conclusion: One- and two-level ACDF with standalone PEEK cages provided high fusion rates. Surgical spondylosis contributed to a reduction of spinal mobility despite the hypermobility in adjacent spinal segments. No degeneration in adjacent spinal segments was documented within a year of ACDF, and the treatment seemed to improve patients' quality of life.
MeSH term(s)	Cervical Vertebrae/surgery ; Diskectomy ; Humans ; Intervertebral Disc Degeneration ; Ketones ; Polyethylene Glycols ; Quality of Life ; Retrospective Studies ; Spinal Fusion ; Treatment Outcome
Chemical Substances	Ketones ; polyetheretherketone (31694-16-3) ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2019-09-20
Publishing country	Poland
Document type	Journal Article
ZDB-ID	415519-1
ISSN	1897-4260 ; 0028-3843
ISSN (online)	1897-4260
ISSN	0028-3843
DOI	10.5603/PJNNS.a2019.0040
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Article: Topografia i morfometria otworu jamy nerwu trójdzielnego.

Mariak, Zenon

Neurologia i neurochirurgia polska

2006 Volume 40, Issue 6, Page(s) 539; author reply 539–40

Title translation	Topography and morphometry of trigeminal nerve opening.
MeSH term(s)	Cerebellopontine Angle/anatomy & histology ; Cerebral Veins/anatomy & histology ; Dura Mater/anatomy & histology ; Humans ; Ligaments/anatomy & histology ; Skull Base/anatomy & histology ; Terminology as Topic ; Trigeminal Nerve/anatomy & histology
Language	Polish
Publishing date	2006-11
Publishing country	Poland
Document type	Comment ; Letter
ZDB-ID	415519-1
ISSN	1897-4260 ; 0028-3843
ISSN (online)	1897-4260
ISSN	0028-3843
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Article ; Online: Clinical Prognosis for SAH Consistent with Redox Imbalance and Lipid Peroxidation.

Jarocka-Karpowicz, Iwona / Syta-Krzyżanowska, Anna / Kochanowicz, Jan / Mariak, Zenon Dionizy

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 8

Abstract: Subarachnoid hemorrhage (SAH) accounts for 3% of all strokes. As more and more data indicates the role of oxidative stress in acute brain damage caused by SAH, an attempt was made to correlate the clinical status of patients with systemic level of ... ...

Abstract	Subarachnoid hemorrhage (SAH) accounts for 3% of all strokes. As more and more data indicates the role of oxidative stress in acute brain damage caused by SAH, an attempt was made to correlate the clinical status of patients with systemic level of antioxidants and lipid peroxidation products. The hemorrhage was diagnosed with brain computed tomography (CT) and aneurysm with angio-CT and angiography, while the vasospasm was monitored with transcranial Doppler. Plasma glutathione peroxidase activity (GSH-Px) and vitamin A, E, and C levels were determined spectrophotometrically and by HPLC, respectively. The levels of polyunsaturated fatty acids (PUFAs) cyclization products were determined by GC-MS, while F
MeSH term(s)	Adult ; Aged ; Antioxidants ; Biomarkers ; Female ; Humans ; Lipid Metabolism ; Lipid Peroxidation ; Lipids/blood ; Male ; Middle Aged ; Oxidation-Reduction ; Oxidative Stress ; Prognosis ; Reactive Oxygen Species/metabolism ; Severity of Illness Index ; Subarachnoid Hemorrhage/blood ; Subarachnoid Hemorrhage/diagnosis ; Subarachnoid Hemorrhage/etiology ; Subarachnoid Hemorrhage/metabolism ; Time Factors
Chemical Substances	Antioxidants ; Biomarkers ; Lipids ; Reactive Oxygen Species
Language	English
Publishing date	2020-04-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25081921
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Article ; Online: A comparison of different machine-learning techniques for the selection of a panel of metabolites allowing early detection of brain tumors.

Godlewski, Adrian / Czajkowski, Marcin / Mojsak, Patrycja / Pienkowski, Tomasz / Gosk, Wioleta / Lyson, Tomasz / Mariak, Zenon / Reszec, Joanna / Kondraciuk, Marcin / Kaminski, Karol / Kretowski, Marek / Moniuszko, Marcin / Kretowski, Adam / Ciborowski, Michal

Scientific reports

2023 Volume 13, Issue 1, Page(s) 11044

Abstract: Metabolomics combined with machine learning methods (MLMs), is a powerful tool for searching novel diagnostic panels. This study was intended to use targeted plasma metabolomics and advanced MLMs to develop strategies for diagnosing brain tumors. ... ...

Abstract	Metabolomics combined with machine learning methods (MLMs), is a powerful tool for searching novel diagnostic panels. This study was intended to use targeted plasma metabolomics and advanced MLMs to develop strategies for diagnosing brain tumors. Measurement of 188 metabolites was performed on plasma samples collected from 95 patients with gliomas (grade I-IV), 70 with meningioma, and 71 healthy individuals as a control group. Four predictive models to diagnose glioma were prepared using 10 MLMs and a conventional approach. Based on the cross-validation results of the created models, the F1-scores were calculated, then obtained values were compared. Subsequently, the best algorithm was applied to perform five comparisons involving gliomas, meningiomas, and controls. The best results were obtained using the newly developed hybrid evolutionary heterogeneous decision tree (EvoHDTree) algorithm, which was validated using Leave-One-Out Cross-Validation, resulting in an F1-score for all comparisons in the range of 0.476-0.948 and the area under the ROC curves ranging from 0.660 to 0.873. Brain tumor diagnostic panels were constructed with unique metabolites, which reduces the likelihood of misdiagnosis. This study proposes a novel interdisciplinary method for brain tumor diagnosis based on metabolomics and EvoHDTree, exhibiting significant predictive coefficients.
MeSH term(s)	Humans ; Brain Neoplasms/diagnosis ; Brain Neoplasms/pathology ; Glioma/pathology ; Brain/metabolism ; Meningioma/diagnosis ; Meningioma/pathology ; Machine Learning ; Meningeal Neoplasms
Language	English
Publishing date	2023-07-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-38243-1
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