Publications

Generation of DMBi002-A human induced pluripotent stem cell line from patient with Spinal muscular atrophy type 3

Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disease caused by mutations inSMN1 gene encoding survival motor neuron (SMN) protein. Lack of this protein leads to progressive loss of motor neurons and therefore to gradual loss of signal transmission between motor neurons and skeletal muscle cells. As a consequence, patients develop muscle atrophy and lose the ability to move independently, what is also related to problems with breathing and swallowing. Here, we describe the generation of human induced pluripotent stem cells (hiPSC) from peripheral blood mononuclear cells (PBMC) of adult SMA type 3 patient with a use of Sendai virus vectors.

Supplementary Figure 4 from Hypoxia-Regulated Overexpression of Soluble VEGFR2 Controls Angiogenesis and Inhibits Tumor Growth

<p>PDF - 2705KB, Expression of VEGFRs on the surface of B16F10-msVEGFR2 melanoma clone 13.3 and 16.4.</p>

15-Deoxy-Δ12,14-prostaglandin-J2 inhibits expression of eNOS in human endothelial cells

Complex effect of atorvastatin on angiogenic gene expression in normoxic and hypoxic microvascular endothelial cells

Photodynamic therapy-driven induction of suicide cytosine deaminase gene

Supplementary Figure 3 from Hypoxia-Regulated Overexpression of Soluble VEGFR2 Controls Angiogenesis and Inhibits Tumor Growth

<p>PDF - 2157KB, Characterization of the transfected clones for msVEGFR2 and mVEGF-A production.</p>

Targeted expression of heme oxygenase-1 in satellite cells improves skeletal muscle pathology in dystrophic mice

Comment on “A Novel Role of Hypoxia-Inducible Factor in Cobalt Chloride- and Hypoxia-Mediated Expression of IL-8 Chemokine in Human Endothelial Cells”

Kidney injury by cyclosporine A is aggravated in heme oxygenase-1 deficient mice and involves regulation of microRNAs

Cyclosporine A (CsA), a widely used immunosuppressive drug, exerts nephrotoxic activities, as demonstrated by increased tubulointerstitial fibrosis, inflammation and podocyte damage. Recently, a number of microRNAs expressed in the kidney have been reported to be elevated during renal damage. Our aim was to investigate the effect of CsA on selected microRNAs in the mouse kidney after CsA treatment. Moreover, as heme oxygenase-1 (HO-1, encoded by the Hmox1 gene) was shown to play a protective role during kidney disorders, we assessed whether HO-1 deficiency in vivo influences the CsA-regulated microRNAs’ expression. We have observed that the pro-fibrotic miR-21 and pro-apoptotic miR-34a expression was upregulated in kidneys of HO-1 deficient mice and it was further enhanced by CsA. Concomitantly, the level of anti-fibrotic microRNAs, belonging to miR-29 and miR-200 families, was down-regulated after CsA treatment. Generally, Hmox1 knock-out (Hmox1–/–) animals were more susceptible to CsA treatment, as the mortality rate was 4 out of 9 Hmox1–/– mice, and increased fibrosis (Tgfb2, Pai1), inflammation (Il6) and apoptosis (Cdkn1a-p21) were noticed in the HO-1 deficient kidneys. In summary, our data demonstrate that CsA induces significant changes in the expression of renal microRNAs and emphasize HO-1 deficiency as an important factor contributing to the CsA-mediated renal toxicity.

Regulation of inducible nitric oxide synthase (iNOS) and GTP cyclohydrolase I (GTP-CH I) gene expression by ox-LDL in rat vascular smooth muscle cells.

The generation of nitric oxide is regulated by several factors, including the substrates and cofactors supplementation. Decreased expression and activity of nitric oxide synthase as well as diminished amount of L-arginine or enzyme cofactors results in the inhibition of nitric oxide generation in vascular wall cells. GTP cyclohydrolase 1 is a key enzyme involved in the synthesis of tetrahydrobiopterin, one of the most important cofactors of NO synthases. We have demonstrated that oxidized LDL inhibit not only inducible nitric oxide synthase gene expression but also GTP cyclohydrolase I gene expression in interleukin-1 beta activated rat vascular smooth muscle cells in vitro. It is postulated that diminished availability of tetrahydrobiopterin may additionally impair the generation of nitric oxide in atherosclerosis.

Attenuation of Nrf2 expression and antioxidant response by ochratoxin A - the impact on the profibrotic effect

Ochratoxin A (OTA), a nephrotoxic mycotoxin, is considered as a causal agent of Balkan endemic nephropathy (BEN), a chronic kidney disease. Generation of oxidative stress by OTA has been suggested as one of the mechanisms implicated in its genotoxicity and cytotoxicity. Oxidative stress in cells activates expression of superoxide dismutase (SOD), glutathione-S-transferase (GST) and heme oxygenase (HO), the protective enzymes, expression of which is regulated by nuclear factor – erythroid 2 related factor (Nrf2) transcription factor. In cultured kidney tubulus cells (LLC-PK1) OTA diminished antioxidant response via attenuation of Nrf2, SOD, GST and HO expression. Moreover, this mycotoxin potently elevated expression of profibrotic agents: transforming growth factors-b (TGFb1 and TGFb2) with concomitant decrease in expression of proangiogenic genes, like vascular endothelial growth factor (VEGF) and erythropoietin (Epo). Adenoviral vectors were used to investigate the role of Nrf2 and HO-1 in OTA-induced toxicity. Overexpression of Nrf2 as well as application of pharmacological inducer of Nrf2 (PGJ2) led to attenuation of OTA-elevated TGFb expression and caused increase of OTA-diminished HO-1 and Epo mRNA level. However, genetic overexpression of HO1 did not prevent OTAinduced alterations. The phosphorylation of MAP kinases – JNK and ERK42/44 after OTA treatment was observed, and pharmacological inhibition of ERK42/44 compensated the effect of OTA on TGFb2 expression. Present data indicate the attenuation of antioxidant response as one of the mechanisms of OTA action. Nrf2 overexpression can compensate some but not all of OTAevoked alterations. Nevertheless, Nrf2 may be considered as one of the important factors in antifibrotic therapy.

Supplementary Figure 1 from Hypoxia-Regulated Overexpression of Soluble VEGFR2 Controls Angiogenesis and Inhibits Tumor Growth

<p>PDF - 86KB, Construction maps for the pIFP1.4-HREmsVEGFR2 and pHREmsVEGFR2 vector,</p>

P254Comparison of the transcriptome of human mesenchymal cells isolated from right ventricle and epicardial fat

contribute to the complex phenotype.Further comprehensive functional studies are required to evaluate the possible role of SYNM mutations in development of ulnar-mammary syndrome and ventricular arrhythmias. P251Genomic microimbalances in children with combined congenital heart and kidney defects

Heme oxygenase-1 inhibits microRNA biogenesis and impairs myogenesis

Angiogenesis, stem cells, eNOS and inflammation – the many faces of vascular biology

No abstract available.

Influence of oxy-LDL and interleukin-8 on the platelet/PMNs adhesion and on chemotaxis-mediated induction of iNOS in neutrophils.

Selectin-P expression on platelets stimulated with thrombin was measured in terms of formation of "rosettes" according to Jungi et al. [9]. Selectin-P-mediated platelet/PMNs adhesion was inhibited by iloprost (IC50 = 5.0 nM), sodium nitroprusside (NaNP, IC50 = 0.93 microM) and interleukin-8 (IL-8, IC50 = 88 ng/ml), but activated dose-dependently by oxy-LDL (3-15 micrograms/ml). Glycogen-induced peritonitis in rats up-regulated the iNOS activity measured by the 2,3-[3H]-citrulline formation by the abdominal cavity PMNs up to 6 h after insult. Pretreatment with IL-8 (3 micrograms/300 g iv) decreased the amount of PMNs in ascites as well as its iNOS activity. Chemotaxis mediated iNOS gene expression of PMNs were measured by Northern blot hybridization. IL-8 (100 ng/ml) did not influence the PMNs iNOS gene expression induced by chemotaxis. We conclude that the decrease in iNOS activity by IL-8 involves postranslational modification of the enzyme activity.

DYRK1A Kinase Inhibitors Promote β-Cell Survival and Insulin Homeostasis

The rising prevalence of diabetes is threatening global health. It is known not only for the occurrence of severe complications but also for the SARS-Cov-2 pandemic, which shows that it exacerbates susceptibility to infections. Current therapies focus on artificially maintaining insulin homeostasis, and a durable cure has not yet been achieved. We demonstrate that our set of small molecule inhibitors of DYRK1A kinase potently promotes β-cell proliferation, enhances long-term insulin secretion, and balances glucagon level in the organoid model of the human islets. Comparable activity is seen in INS-1E and MIN6 cells, in isolated mice islets, and human iPSC-derived β-cells. Our compounds exert a significantly more pronounced effect compared to harmine, the best-documented molecule enhancing β-cell proliferation. Using a body-like environment of the organoid, we provide a proof-of-concept that small–molecule–induced human β-cell proliferation via DYRK1A inhibition is achievable, which lends a considerable promise for regenerative medicine in T1DM and T2DM treatment.

Cukrzyca typu 2 upośledza funkcjonowanie komórek śródbłonka