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Authors = Justyna Janik

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20 pages, 3550 KiB  
Article
Immobilisation of Cellobiose Dehydrogenase and Laccase on Chitosan Particles as a Multi-Enzymatic System for the Synthesis of Lactobionic Acid
by Justyna Sulej, Wiktoria Piątek-Gołda, Marcin Grąz, Katarzyna Szałapata, Piotr Waśko, Ewa Janik-Zabrotowicz and Monika Osińska-Jaroszuk
J. Funct. Biomater. 2023, 14(7), 383; https://doi.org/10.3390/jfb14070383 - 21 Jul 2023
Cited by 8 | Viewed by 2277
Abstract
Lactobionic acid (LBA) is a bioactive compound that has become increasingly popular in medicine in recent years due to its unique properties. This chemical can be formed via the enzymatic oxidation of lactose using fungal oxidoreductive enzymes. This study aimed to intensify the [...] Read more.
Lactobionic acid (LBA) is a bioactive compound that has become increasingly popular in medicine in recent years due to its unique properties. This chemical can be formed via the enzymatic oxidation of lactose using fungal oxidoreductive enzymes. This study aimed to intensify the synthesis of LBA using immobilised enzymes (cellobiose dehydrogenase from Phanerochaete chrysosporium (PchCDH) and laccase from Cerrena unicolor (CuLAC)) on chitosan microspheres. We used three different crosslinking agents: genipin, glutaraldehyde, and polyethyleneimine to activate the chitosan. The FTIR and CellDrop techniques were used to characterise the activated microspheres. Quantitative (HPLC) and qualitative (TLC) methods were used to determine the obtained LBA. The results show that the type of activator used influences the efficiency of the binding of the enzyme to the matrix. Furthermore, the amount of LBA formed depends on the type of system used. The use of a system in which one of the enzymes is immobilised on a PEI-activated carrier (PchCDH) and the other is free (CuLAC) proved to be the most optimal, as it yielded almost 100% conversion of lactose to lactobionic acid. Summarising the data obtained the following: lactobionic acid immobilised on chitosan microspheres has great potential for medical applications. Full article
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7 pages, 439 KiB  
Article
The Impact of Amortization of Gene Therapies Funding on the Results and Conclusions of CEMs and BIMs
by Hubert Polek, Justyna Janik, Ewelina Paterak, Monique Dabbous, Michał Pochopień and Mondher Toumi
J. Mark. Access Health Policy 2023, 11(1), 2232648; https://doi.org/10.1080/20016689.2023.2232648 - 10 Jul 2023
Viewed by 1119
Abstract
ABSTRACT Background: Gene replacement therapy (GRT) is a treatment method used to combat or prevent various diseases. Its high one-off cost constitutes a major obstacle for successful market access. This paper aims to assess and discuss the applicability of amortization in models, [...] Read more.
ABSTRACT Background: Gene replacement therapy (GRT) is a treatment method used to combat or prevent various diseases. Its high one-off cost constitutes a major obstacle for successful market access. This paper aims to assess and discuss the applicability of amortization in models, such as cost-effectiveness models (CEMs) and budget impact models (BIMs) informing HTA recommendations and reimbursement decisions. Methods and findings: A hypothetical CEA and BIA were considered. The objective was to compare the GRT with and without amortization. A straight-line amortization model was used. The CEM and BIM were considered and assessed based on two set of scenarios: considering different amortization duration or different discounting rate. The impact of amortization against the total cost of gene therapy was assessed for all the scenarios. The cost difference between GRT with and without amortization in relation to its total cost was -$58,855, thus amortization does not have a significant impact on the results and conclusions of the cost-effectiveness analysis. For BIM in the base case, amortization had no impact on the results. Conclusion: Amortization has negligible impact on the results of CEM and total BIM and no impact on the conclusions from the model. One exception is the budget impact in case of an amortization period longer than the time horizon of BIM, where a half of the GRT price is moved beyond the model time horizon. Amortization has a distinguishing effect from an accounting perspective, but it does not have any implication for payers. Full article
17 pages, 3691 KiB  
Article
Multi-Enzymatic Synthesis of Lactobionic Acid Using Wood-Degrading Enzymes Produced by White Rot Fungi
by Wiktoria Piątek-Gołda, Justyna Sulej, Marcin Grąz, Piotr Waśko, Ewa Janik-Zabrotowicz and Monika Osińska-Jaroszuk
Metabolites 2023, 13(4), 469; https://doi.org/10.3390/metabo13040469 - 24 Mar 2023
Cited by 2 | Viewed by 3177
Abstract
Enzymes produced by white rot fungi are involved in the synthesis of secondary metabolites with valuable biotechnological properties. One of these metabolites is lactobionic acid (LBA). The aim of this study was to characterize a novel enzyme system consisting of a cellobiose dehydrogenase [...] Read more.
Enzymes produced by white rot fungi are involved in the synthesis of secondary metabolites with valuable biotechnological properties. One of these metabolites is lactobionic acid (LBA). The aim of this study was to characterize a novel enzyme system consisting of a cellobiose dehydrogenase from Phlebia lindtneri (PlCDH), a laccase from Cerrena unicolor (CuLAC), a redox mediator (ABTS or DCPIP), and lactose as a substrate. We used quantitative (HPLC) and qualitative methods (TLC, FTIR) to characterise the obtained LBA. The free radical scavenging effect of the synthesised LBA was assessed with the DPPH method. Bactericidal properties were tested against Gram-negative and Gram-positive bacteria. We obtained LBA in all the systems tested; however, the study showed that the temperature of 50 °C with the addition of ABTS was the most advantageous condition for the synthesis of lactobionic acid. A mixture with 13 mM LBA synthesised at 50 °C with DCPIP showed the best antioxidant properties (40% higher compared with the commercial reagent). Furthermore, LBA had an inhibitory effect on all the bacteria tested, but the effect was better against Gram-negative bacteria with growth inhibition no lower than 70%. Summarizing the obtained data, lactobionic acid derived in a multienzymatic system is a compound with great biotechnological potential. Full article
(This article belongs to the Special Issue Secondary Metabolites in Fungi-Plant Interactions)
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22 pages, 13598 KiB  
Article
Determination and Removal of Selected Pharmaceuticals and Total Organic Carbon from Surface Water by Aluminum Chlorohydrate Coagulant
by Joanna Kuc, Maciej Thomas, Iwona Grochowalska, Rafał Kulczyk, Gabriela Mikosz, Fabian Mrózek, Dagmara Janik, Justyna Korta and Karolina Cwynar
Molecules 2022, 27(17), 5740; https://doi.org/10.3390/molecules27175740 - 5 Sep 2022
Cited by 10 | Viewed by 2995
Abstract
In the present research, the removal of Total Organic Carbon (TOC) and erythromycin (ERY), fluoxetine (FLX), amoxicillin (AMO), colistin (COL), ethynylestradiol (EE), and diclofenac (DIC) from surface water by coagulation is studied. The concentration of selected pharmaceuticals in 24 surface water samples originating [...] Read more.
In the present research, the removal of Total Organic Carbon (TOC) and erythromycin (ERY), fluoxetine (FLX), amoxicillin (AMO), colistin (COL), ethynylestradiol (EE), and diclofenac (DIC) from surface water by coagulation is studied. The concentration of selected pharmaceuticals in 24 surface water samples originating from some rivers located in Lesser Poland Voivodeship and Silesia Voivodeship, Poland, was determined. The removal of TOC and pharmaceuticals was carried out using the application of Design of Experiments (DOE), Response Surface Methodology (RSM), and by addition of aluminum chlorohydrate (ACH) as a coagulant. The study found that the concentration ranges of ERY, FLX, AMO, COL, EE, and DIC in analyzed water samples were 7.58–412.32, 1.21–72.52, 1.22–68.55, 1.28–32.01, 5.36–45.56, 2.20–182.22 ng/L, respectively. In some cases, concentrations lower than 1 ng/L were determined. In optimal conditions of coagulation process of spiked surface water (pH = 6.5 ± 0.1, ACH dose = 0.35 mL/L, Time = 30 min; R2 = 0.8799, R2adj = 0.7998), the concentration of TOC, ERY, FLX, AMO, COL, EE, and DIC was decreased by 88.7, 36.4, 24.7, 29.0, 25.5, 35.4, 30.4%, respectively. Simultaneously, turbidity, color, Total Suspended Solids (TSS), Chemical Oxygen Demand (COD), Total Nitrogen (Total N), and Ammonium-Nitrogen (N-NH4) were decreased by 96.2%, >98.0%, 97.8%, 70.0%, 88.7%, 37.5%, respectively. These findings suggest that ACH may be an optional reagent to remove studied pharmaceuticals from contaminated water. Full article
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16 pages, 3897 KiB  
Article
Synthesis of Dolichols in Candida albicans Is Co-Regulated with Elongation of Fatty Acids
by Anna Janik, Urszula Perlińska-Lenart, Katarzyna Gawarecka, Justyna Augustyniak, Ewelina Bratek-Gerej, Przemysław Bernat, Sebastian Piłsyk, Patrycja Skalmowska, Grażyna Palamarczyk, Ewa Swiezewska and Joanna S. Kruszewska
Int. J. Mol. Sci. 2022, 23(1), 409; https://doi.org/10.3390/ijms23010409 - 30 Dec 2021
Cited by 3 | Viewed by 4276
Abstract
Protein glycosylation requires dolichyl phosphate as a carbohydrate carrier. Dolichols are α-saturated polyprenols, and their saturation in S. cerevisiae is catalyzed by polyprenyl reductase Dfg10 together with some other unknown enzymes. The aim of this study was to identify such enzymes in Candida [...] Read more.
Protein glycosylation requires dolichyl phosphate as a carbohydrate carrier. Dolichols are α-saturated polyprenols, and their saturation in S. cerevisiae is catalyzed by polyprenyl reductase Dfg10 together with some other unknown enzymes. The aim of this study was to identify such enzymes in Candida. The Dfg10 polyprenyl reductase from S. cerevisiae comprises a C-terminal 3-oxo-5-alpha-steroid 4-dehydrogenase domain. Alignment analysis revealed such a domain in two ORFs (orf19.209 and orf19.3293) from C. albicans, which were similar, respectively, to Dfg10 polyprenyl reductase and Tsc13 enoyl-transferase from S. cerevisiae. Deletion of orf19.209 in Candida impaired saturation of polyprenols. The Tsc13 homologue turned out not to be capable of saturating polyprenols, but limiting its expression reduce the cellular level of dolichols and polyprenols. This reduction was not due to a decreased expression of genes encoding cis-prenyltransferases from the dolichol branch but to a lower expression of genes encoding enzymes of the early stages of the mevalonate pathway. Despite the resulting lower consumption of acetyl-CoA, the sole precursor of the mevalonate pathway, it was not redirected towards fatty acid synthesis or elongation. Lowering the expression of TSC13 decreased the expression of the ACC1 gene encoding acetyl-CoA carboxylase, the key regulatory enzyme of fatty acid synthesis and elongation. Full article
(This article belongs to the Section Molecular Biology)
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18 pages, 417 KiB  
Review
An Overview of Health Technology Assessments of Gene Therapies with the Focus on Cost-Effectiveness Models
by Michał Pochopień, Ewelina Paterak, Emilie Clay, Justyna Janik, Samuel Aballea, Małgorzata Biernikiewicz and Mondher Toumi
J. Mark. Access Health Policy 2021, 9(1), 2002006; https://doi.org/10.1080/20016689.2021.2002006 - 13 Nov 2021
Cited by 14 | Viewed by 893
Abstract
Background: Gene therapies can treat, prevent, or cure a disease by changing the expression of a person’s genes. They are an innovative strategy for treating genetic disorders; however, they are still emerging on the market access and in the healthcare system. Health technology [...] Read more.
Background: Gene therapies can treat, prevent, or cure a disease by changing the expression of a person’s genes. They are an innovative strategy for treating genetic disorders; however, they are still emerging on the market access and in the healthcare system. Health technology assessment (HTA) agencies have not yet elaborated any standardised approach for assessing gene therapies; therefore, significant differences can be seen during HTAs carried out in various countries. In this review, we focused on submitted economic models of gene therapies approved for use by the US FDA and EMA with the aim to provide a comprehensive summary of how selected HTA bodies assessed the cost-effectiveness of gene therapies. An additional objective was to examine and discuss differences in the methods used in economic models across countries and drugs. Methods: We identified economic models of gene therapies from six countries (NICE, IQWiG, SMC, HAS, CADTH, ICER) and focused on nine agents (Glybera, Imlygic, Strimvelis, Yescarta, Kymriah, Luxturna, Zynteglo, Zolgensma, Tecartus). Details of cost-utility evaluations and budget impact models were reviewed and extracted. Results: Overall, 983 publications were identified, and 17 studies were included for the analysis. Reviewed evaluations of gene therapies differed in terms of the study perspective, discounting, extrapolation of outcomes based on limited and immature data, time horizon, and adequate estimation of benefits in terms of quality-adjusted life-years. Methods of economic evaluations were in line with the current recommendations; however, long-term follow-up studies are still missing. Conclusions: Discrepancies in an economic evaluation of gene therapies between different HTA bodies are rooted in a lack of general assessment frameworks specific to gene therapies. Although challenges were resolved by adjustments to the currently used value assessment framework, new methodological approaches would be useful. In addition, to improve the methods and quality of an evaluation, further research would be valuable. Full article
22 pages, 41297 KiB  
Article
Processing of Polyester-Urethane Filament and Characterization of FFF 3D Printed Elastic Porous Structures with Potential in Cancellous Bone Tissue Engineering
by Agnieszka Haryńska, Iga Carayon, Paulina Kosmela, Anna Brillowska-Dąbrowska, Marcin Łapiński, Justyna Kucińska-Lipka and Helena Janik
Materials 2020, 13(19), 4457; https://doi.org/10.3390/ma13194457 - 8 Oct 2020
Cited by 29 | Viewed by 4693
Abstract
This paper addresses the potential of self-made polyester-urethane filament as a candidate for Fused Filament Fabrication (FFF)-based 3D printing (3DP) in medical applications. Since the industry does not provide many ready-made solutions of medical-grade polyurethane filaments, we undertook research aimed at presenting the [...] Read more.
This paper addresses the potential of self-made polyester-urethane filament as a candidate for Fused Filament Fabrication (FFF)-based 3D printing (3DP) in medical applications. Since the industry does not provide many ready-made solutions of medical-grade polyurethane filaments, we undertook research aimed at presenting the process of thermoplastic polyurethane (TPU) filament formation, detailed characteristics, and 3DP of specially designed elastic porous structures as candidates in cancellous tissue engineering. Additionally, we examined whether 3D printing affects the structure and thermal stability of the filament. According to the obtained results, the processing parameters leading to the formation of high-quality TPU filament (TPU_F) were captured. The results showed that TPU_F remains stable under the FFF 3DP conditions. The series of in vitro studies involving long- and short-term degradation (0.1 M phosphate-buffered saline (PBS); 5 M sodium hydroxide (NaOH)), cytotoxicity (ISO 10993:5) and bioactivity (simulated body fluid (SBF) incubation), showed that TPU printouts possessing degradability of long-term degradable tissue constructs, are biocompatible and susceptible to mineralization in terms of hydroxyapatite (HAp) formation during SBF exposure. The formation of HAp on the surface of the specially designed porous tissue structures (PTS) was confirmed by scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) studies. The compression test of PTS showed that the samples were strengthened due to SBF exposure and deposited HAp on their surface. Moreover, the determined values of the tensile strength (~30 MPa), Young’s modulus (~0.2 GPa), and compression strength (~1.1 MPa) allowed pre-consideration of TPU_F for FFF 3DP of cancellous bone tissue structures. Full article
(This article belongs to the Special Issue Additive Manufacturing (AM) of Biomaterials)
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18 pages, 10784 KiB  
Article
Medical-Grade PCL Based Polyurethane System for FDM 3D Printing—Characterization and Fabrication
by Agnieszka Haryńska, Justyna Kucinska-Lipka, Agnieszka Sulowska, Iga Gubanska, Marcin Kostrzewa and Helena Janik
Materials 2019, 12(6), 887; https://doi.org/10.3390/ma12060887 - 16 Mar 2019
Cited by 108 | Viewed by 11341
Abstract
The widespread use of three-dimensional (3D) printing technologies in medicine has contributed to the increased demand for 3D printing materials. In addition, new printing materials that are appearing in the industry do not provide a detailed material characterization. In this paper, we present [...] Read more.
The widespread use of three-dimensional (3D) printing technologies in medicine has contributed to the increased demand for 3D printing materials. In addition, new printing materials that are appearing in the industry do not provide a detailed material characterization. In this paper, we present the synthesis and characterization of polycaprolactone (PCL) based medical-grade thermoplastic polyurethanes, which are suitable for forming in a filament that is dedicated to Fused Deposition Modeling 3D (FDM 3D)printers. For this purpose, we synthesized polyurethane that is based on PCL and 1,6-hexamethylene diisocyanate (HDI) with a different isocyanate index NCO:OH (0.9:1, 1.1:1). Particular characteristics of synthesized materials included, structural properties (FTIR, Raman), thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)), mechanical and surfaces (contact angle) properties. Moreover, pre-biological tests in vitro and degradation studies were also performed. On the basis of the conducted tests, a material with more desirable properties S-TPU(PCL)0.9 was selected and the optimization of filament forming via melt-extrusion process was described. The initial biological test showed the biocompatibility of synthesized S-TPU(PCL)0.9 with respect to C2C12 cells. It was noticed that the process of thermoplastic polyurethanes (TPU) filaments forming by extrusion was significantly influenced by the appropriate ratio between the temperature profile, rotation speed, and dosage ratio. Full article
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19 pages, 5463 KiB  
Article
Fabrication and Characterization of Flexible Medical-Grade TPU Filament for Fused Deposition Modeling 3DP Technology
by Agnieszka Haryńska, Iga Gubanska, Justyna Kucinska-Lipka and Helena Janik
Polymers 2018, 10(12), 1304; https://doi.org/10.3390/polym10121304 - 25 Nov 2018
Cited by 98 | Viewed by 11358
Abstract
The possibility of using additive manufacturing (AM) in the medicine area has created new opportunities in health care. This has contributed to a sharp increase in demand for 3D printers, their systems and materials that are adapted to strict medical requirements. We described [...] Read more.
The possibility of using additive manufacturing (AM) in the medicine area has created new opportunities in health care. This has contributed to a sharp increase in demand for 3D printers, their systems and materials that are adapted to strict medical requirements. We described herein a medical-grade thermoplastic polyurethane (S-TPU) which was developed and then formed into a filament for Fused Deposition Modeling (FDM) 3D printers during a melt-extrusion process. S-TPU consisting of aliphatic hexamethylene 1,6-diisocyanate (HDI), amorphous α,ω-dihydroxy(ethylene-butylene adipate) (PEBA) and 1,4 butandiol (BDO) as a chain extender, was synthesized without the use of a catalyst. The filament (F-TPU) properties were characterized by rheological, mechanical, physico-chemical and in vitro biological properties. The tests showed biocompatibility of the obtained filament as well as revealed no significant effect of the filament formation process on its properties. This study may contribute to expanding the range of medical-grade flexible filaments for standard low-budget FDM printers. Full article
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21 pages, 11590 KiB  
Article
The Influence of Calcium Glycerophosphate (GPCa) Modifier on Physicochemical, Mechanical, and Biological Performance of Polyurethanes Applicable as Biomaterials for Bone Tissue Scaffolds Fabrication
by Justyna Kucińska-Lipka, Iga Gubanska, Olexandr Korchynskyi, Khrystyna Malysheva, Marcin Kostrzewa, Damian Włodarczyk, Jakub Karczewski and Helena Janik
Polymers 2017, 9(8), 329; https://doi.org/10.3390/polym9080329 - 1 Aug 2017
Cited by 14 | Viewed by 6535
Abstract
In this paper we describe the synthesis of poly(ester ether urethane)s (PEEURs) by using selected raw materials to reach a biocompatible polyurethane (PU) for biomedical applications. PEEURs were synthesized by using aliphatic 1,6-hexamethylene diisocyanate (HDI), poly(ethylene glycol) (PEG), α,ω-dihydroxy(ethylene-butylene adipate) (Polios), 1,4-butanediol (BDO) [...] Read more.
In this paper we describe the synthesis of poly(ester ether urethane)s (PEEURs) by using selected raw materials to reach a biocompatible polyurethane (PU) for biomedical applications. PEEURs were synthesized by using aliphatic 1,6-hexamethylene diisocyanate (HDI), poly(ethylene glycol) (PEG), α,ω-dihydroxy(ethylene-butylene adipate) (Polios), 1,4-butanediol (BDO) as a chain extender and calcium glycerolphosphate salt (GPCa) as a modifier used to stimulate bone tissue regeneration. The obtained unmodified (PURs) and modified with GPCa (PURs-M) PEEURs were studied by various techniques. It was confirmed that urethane prepolymer reacts with GPCa modifier. Further analysis of the obtained PURs and PURs-M by Fourier transform infrared (FTIR) and Raman spectroscopy revealed the chemical composition typical for PUs by the confirmed presence of urethane bonds. Moreover, the FTIR and Raman spectra indicated that GPCa was incorporated into the main PU chain at least at one-side. The scanning electron microscopy (SEM) analysis of the PURs-M surface was in good agreement with the FTIR and Raman analysis due to the fact that inclusions were observed only at 20% of its surface, which were related to the non-reacted GPCa enclosed in the PUR matrix as filler. Further studies of hydrophilicity, mechanical properties, biocompatibility, short term-interactions, and calcification study lead to the final conclusion that the obtained PURs-M may by suitable candidate material for further scaffold fabrication. Scaffolds were prepared by the solvent casting/particulate leaching technique (SC/PL) combined with thermally-induced phase separation (TIPS). Such porous scaffolds had satisfactory pore sizes (36–100 μm) and porosity (77–82%) so as to be considered as suitable templates for bone tissue regeneration. Full article
(This article belongs to the Special Issue Advance of Polymers Applied to Biomedical Applications: Biointerface)
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