A5008639139- Genomics, phytochemicals, and oxidative stress
- Aortic aneurysm repair treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Glutathione Transferases and Polymorphisms
- COVID-19 Clinical Research Studies
- Adipose Tissue and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Mathematical Biology Tumor Growth
- ATP Synthase and ATPases Research
- Alcohol Consumption and Health Effects
- Peripheral Artery Disease Management
- Angiogenesis and VEGF in Cancer
- Climate Change and Health Impacts
- Aortic Disease and Treatment Approaches
- Redox biology and oxidative stress
- IL-33, ST2, and ILC Pathways
- Neonatal Health and Biochemistry
- Cancer Cells and Metastasis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- MicroRNA in disease regulation
- Cell death mechanisms and regulation
- Immune cells in cancer
- Effects of Radiation Exposure
- SARS-CoV-2 and COVID-19 Research
- Spinal Cord Injury Research
Jagiellonian University
2016-2025
Manchester Metropolitan University
2016
Abstract Endothelial cells (ECs) play a crucial role in the development and propagation of severe COVID-19 stage as well multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by infection ECs with SARS-CoV-2 or via indirect mechanisms. One major concerns raised contradictory data supporting denying presence ACE2, binding receptor, on EC surface. Here, we show that primary human pulmonary artery possess ACE2 capable...
Degradation during production and delivery is a significant bottleneck in developing biomolecular therapies. Here, we show that encapsulation protein cages formed by engineered variants of cage-forming lumazine synthase establishes an effective route for microbial isolation otherwise difficult-to-express, degradation-prone polypeptides. In this system, genetic fusion to cage component protomer ensures efficient guest packaging while being produced host bacterial cells. Meanwhile, the...
Epidemiologic studies suggest that diabetes is associated with an increased risk of cancer. Concurrently, clinical trials have shown metformin, which a first-line antidiabetic drug, displays anticancer activity. The underlying mechanisms for these effects are, however, still not well recognized. Methods based on atomic force microscopy (AFM) were used to directly evaluate the influence metformin nanomechanical and adhesive properties endothelial cancer cells in chronic hyperglycemia. AFM...
Premature senescence, a death escaping pathway for cells experiencing stress, is conducive to aging and cardiovascular diseases. The molecular switch between senescent apoptotic fate remains, however, poorly recognized. Nrf2 an important transcription factor orchestrating adaptive response cellular stress. Here, we show that both human primary endothelial (ECs) murine aortas lacking signaling are but unexpectedly do not encounter damaging oxidative Instead, they exhibit markedly increased...
Heme oxygenase‐1 (HO‐1), encoded by HMOX1 gene and regulated Nrf2 transcription factor, is a cytoprotective enzyme. Its deficiency may exacerbate abdominal aortic aneurysm (AAA) development, which also often associated with hyperlipidemia. Beneficial effects of statins, the broadly used antilipidemic drugs, were attributed to modulation Nrf2/HO‐1 axis. However, effect statins on pathway in patients AAA has not been studied yet. We analyzed tissue from treated simvastatin ( N = 28) or without...
MicroRNA-378a, highly expressed in skeletal muscles, was demonstrated to affect myoblasts differentiation and promote tumour angiogenesis. We hypothesized that miR-378a could play a pro-angiogenic role muscle may be involved regeneration after ischaemic injury mice.Silencing of murine C2C12 did not but impaired their secretory angiogenic potential towards endothelial cells. knockout (miR-378a-/-) mice resulted decreased number CD31-positive blood vessels arterioles gastrocnemius muscle. In...
Surgical intervention is currently the only option for an abdominal aortic aneurysm (AAA), preventing its rupture and sudden death of a patient. Therefore, it crucial to determine pathogenic mechanisms this disease development effective pharmacological therapies. Oxidative stress said be one pivotal factors in pathogenesis AAAs. Thus, we aimed evaluate significance nuclear factor erythroid 2-related 2 (Nrf2) transcriptional activity AAA verify if simvastatin, administered as pre-...
Nrf2 (nuclear factor erythroid 2-like 2) is a transcription known to modulate blood vessel formation. Various experimental settings, however, attribute either stimulatory or repressive influence on angiogenesis. Our findings unveil the mechanism of Nrf2-dependent formation, which reaches beyond transactivation gene expression and reconciles previous discrepancies.We provide evidence that growth differentiation 15 (GDF-15)- stromal cell-derived 1 (SDF-1)-induced angiogenesis strongly depends...
The breach of proteostasis, leading to the accumulation protein aggregates, is a hallmark ageing and age-associated disorders, up now well-established in neurodegeneration. Few studies have addressed issue dysfunctional cell response deposition also for cardiovascular system. However, molecular basis proteostasis decline vascular cells, as well its relation ageing, are not understood. Recent indicated associations Nrf2 transcription factor, critical modulator cellular stress-response, with...
Subcutaneous injection of the tumor cell suspension is a simple and commonly used tool for studying development in vivo. However, subcutaneous models poorly resemble complexity due to fast growth not reflecting natural course. Here, we describe an application new spheroid-plug model combine simplicity with improved resemblance progression. Spheroid-plug relies on vitro formation spheroids, followed by single spheroid subcutaneously Matrigel matrix. In model, tumors grow slower comparison...
Our recent findings indicate that Nrf2 transcriptional activity is essential in maintaining the proper large intestinal structure adult mice. Here, we aimed to verify whether Nrf2-related intestine abnormalities stemmed from early weaning or gestational periods. Therefore, analyzed 4-day-old pups and embryos devoid of (tKO) their wild-type counterparts. We found significant changes tKO including a longer colon, altered crypt distribution, enlargement goblet cells with markedly higher level...
Mesenchymal stromal cells (MSCs) are heterogeneous from adult tissues that able to differentiate in vitro into adipocytes, osteoblasts, or chondrocytes. Such widely studied regenerative medicine. However, the success of cellular therapy depends on cell survival. Heme oxygenase-1 (HO-1, encoded by Hmox1 gene), an enzyme converting heme biliverdin, carbon monoxide, and Fe2+, is cytoprotective can affect stem performance. Therefore, our study aimed at assessing whether critical for survival...
G-quadruplexes (G4) are stacked nucleic acid structures that stabilized by heme. In cells, they affect DNA replication and gene transcription. They unwound several helicases but the composition of repair complex its heme sensitivity unclear. We found accumulation is affected oxygenase-1 (Hmox1) expression, in a cell-type-specific manner: hematopoietic stem cells (HSCs) from Hmox1−/− mice have upregulated expressions G4-unwinding (e.g., Brip1, Pif1) show weaker staining for G-quadruplexes,...
Abdominal aortic aneurysm (AAA) bears a high risk of rupture and sudden death the patient. The pathogenic mechanisms AAA remain elusive, surgical intervention represents only treatment option. Heme oxygenase-1 (HO-1), heme degrading enzyme, is induced in AAA, both mice humans. HO-1 was reported to mitigate development an angiotensin II (AngII)-induced model hyperlipidemic ApoE-/- mice. Since role hyperlipidaemia pathogenesis remains controversial, we aimed evaluate significance progression...
Abstract Clinical data indicate that COVID-19 causes cardiovascular complications, regardless of the severity disease. In this work, we have shown SARS-CoV-2 infection vascular dysfunction due to modification endothelial cell elasticity. We used human pulmonary cells (HPAECs) expressing ACE2 receptor as a model endothelium. This system mimics in vivo conditions, it allows virus entry but not replication. As reference, A549 epithelial cells, well-described supports productive replication...
Targeting of the TRAIL-DR4/5 pathway was proposed as a promising approach for specific induction apoptosis in cancer cells. Clinical trials, however, showed inadequate efficiency TRAIL monotherapy. It is widely held view that application multifunctional molecules or combination therapy may lead to substantial improvement. Here, we demonstrate effectiveness and safety novel chimeric protein, AD-O51.4, which equipped with positively charged VEGFA-derived effector peptides. The study performed...
Myeloid angiogenic cells (MAC) derive from hematopoietic stem/progenitor (HSPCs) that are mobilized the bone marrow. They home to sites of neovascularization and contribute angiogenesis by production paracrine factors. The number function proangiogenic impaired in patients with diabetes or cardiovascular diseases. Both conditions can be accompanied decreased levels heme oxygenase-1 (HMOX1), cytoprotective, heme-degrading enzyme. Our study is aimed at investigating whether precursors myeloid...
Up to date, there is no information on the influence of 2,2,2-tribromoethanol (TBE; Avertin), a commonly used anaesthetic, mice with impaired antioxidant capacity. We aimed analyse effect single dose Avertin anaesthesia duration time, inflammatory response, oxidative stress and collagen deposition in large intestine Nrf2 transcriptional knockout (tNrf2−/−). The studies were performed six-month-old female Nrf2+/+ tNrf2−/− randomly assigned (250 mg/kg b.w. i.p. injection) or vehicle group....