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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 21890

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Special Issue Editors

Prof. Dr. Marek J. Łos

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Guest Editor

Centre of Biotechnology, Silesian University of Technology, 44-100 Gliwice, Poland
Interests: cancer immunology; cell death execution pathways; cancer stem cell biology; epigenetic reprogramming (production of iPS-cells); transdifferentiation technologies; other aspects of regenerative pharmacology
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Wirginia Likus

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Co-Guest Editor

Department of Anatomy, School of Health Sciences in Katowice, Medical University of Silesia, Katowice, Poland
Interests: reconstructive medicine

Special Issue Information

Dear Colleagues,

The 21^st century is witnessing a rapid progress in biotechnology that will likely revolutionize medical interventions not only in the area of transplantology but also in that of drug delivery, with the identification of the most suitable cell subpopulations as primary therapeutic targets in oncology and in tissue regeneration. For example, in 2006 Yamanaka and colleagues developed a technology to produce isogenic (embryonic-like) induced pluripotent stem cells (iPSCs) from somatic cells by the process of reprogramming. iPSCs could then be differentiated into virtually any cell type in the body. In the meantime, an alternative technology of customized cell production from somatic cells through the process of transdifferentiation has progressed. Furthermore, our understanding of the biology of cancer allows for pinpointing cell populations (cancer stem cells, cancer initiating cells, cancer propagating cells) that are responsible for therapeutic failure. On the other hand, in the material science area, new composite materials (biodegradable and non-biodegradable) are being developed that may replace specific components of the connective tissue in different specialized organs. The proposed Special Issue aims to present diverse advances in biotechnology (i) at the level of cell and tissue engineering, (ii) at the level of advanced cancer therapy development, and (iii) at the level of biomaterial and general biotechnology science. Hence, it aims to bridge the gap between the above-mentioned research areas, while presenting specific aspects in an understandable manner to researchers from distinct research fields.

Prof. Dr. Marek J. Łos
Guest Editor
Prof. Dr. Wirginia Likus
Co-Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

stem cells
biomaterials
tissue engineering
reprogramming
transdifferentiation
electrospinning
3D printing

Published Papers (6 papers)

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Research

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21 pages, 5277 KiB

Open AccessArticle

Putative RNA Ligase RtcB Affects the Switch between T6SS and T3SS in Pseudomonas aeruginosa

by Maryam Dadashi, Lin Chen, Ahmad Nasimian, Saeid Ghavami and Kangmin Duan

Int. J. Mol. Sci. 2021, 22(22), 12561; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212561 - 22 Nov 2021

Cited by 5 | Viewed by 2803

Abstract

The opportunistic pathogen Pseudomonas aeruginosa is a significant cause of infection in immunocompromised individuals, cystic fibrosis patients, and burn victims. To benefit its survival, the bacterium adapt to either a motile or sessile lifestyle when infecting the host. The motile bacterium has an often activated type III secretion system (T3SS), which is virulent to the host, whereas the sessile bacterium harbors an active T6SS and lives in biofilms. Regulatory pathways involving Gac-Rsm or secondary messengers such as c-di-GMP determine which lifestyle is favorable for P. aeruginosa. Here, we introduce the RNA binding protein RtcB as a modulator of the switch between motile and sessile bacterial lifestyles. Using the wild-type P. aeruginosa PAO1, and a retS mutant PAO1(∆retS) in which T3SS is repressed and T6SS active, we show that deleting rtcB led to simultaneous expression of T3SS and T6SS in both PAO1(∆rtcB) and PAO1(∆rtcB∆retS). The deletion of rtcB also increased biofilm formation in PAO1(∆rtcB) and restored the motility of PAO1(∆rtcB∆retS). RNA-sequencing data suggested RtcB as a global modulator affecting multiple virulence factors, including bacterial secretion systems. Competitive killing and infection assays showed that the three T6SS systems (H1, H2, and H3) in PAO1(∆rtcB) were activated into a functional syringe, and could compete with Escherichia coli and effectively infect lettuce. Western blotting and RT-PCR results showed that RtcB probably exerted its function through RsmA in PAO1(∆rtcB∆retS). Quantification of c-di-GMP showed an elevated intracellular levels in PAO1(∆rtcB), which likely drove the switch between T6SS and T3SS, and contributed to the altered phenotypes and characteristics observed. Our data demonstrate a pivotal role of RtcB in the virulence of P. aeruginosa by controlling multiple virulence determinants, such as biofilm formation, motility, pyocyanin production, T3SS, and T6SS secretion systems towards eukaryotic and prokaryotic cells. These findings suggest RtcB as a potential target for controlling P. aeruginosa colonization, establishment, and pathogenicity. Full article

(This article belongs to the Special Issue Biotechnology-Recent Advances)

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15 pages, 2822 KiB

Open AccessArticle

Isolation, Culture and Comprehensive Characterization of Biological Properties of Human Urine-Derived Stem Cells

by Martina Culenova, Andreas Nicodemou, Zuzana Varchulova Novakova, Michaela Debreova, Veronika Smolinská, Sona Bernatova, Dana Ivanisova, Olga Novotna, Jaromir Vasicek, Ivan Varga, Stanislav Ziaran and Lubos Danisovic

Int. J. Mol. Sci. 2021, 22(22), 12503; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212503 - 19 Nov 2021

Cited by 8 | Viewed by 3174

Abstract

Mesenchymal stem cells (MSCs) represent an attractive source within the field of tissue engineering. However, their harvesting often requires invasive medical procedures. Urine-derived stem cells (UDSCs) display similar properties to MSCs, and their obtention and further processing is non-invasive for the donors as well as low cost. Here, we offer a comprehensive analysis of their biological properties. The goal of this study was to analyze their morphology, stemness, differentiation potential and cytokine profile. We have successfully isolated UDSCs from 25 urine samples. First colonies emerged up to 9 days after the initial seeding. Cell doubling time was 45 ± 0.24 SD, and when seeded at the density of 100 cells/cm², they formed 42 ± 6.5 SD colonies within 10 days. Morphological analyzes revealed that two different types of the cell populations have been present. The first type had a rice-grain shape and the second one was characterized by a polyhedral shape. In several cell cultures, dome-shaped cells were observed as well. All examined UDSCs expressed typical MSC-like surface markers, CD73, CD90 and CD105. Moreover, conditioned media from UDSCs were harvested, and cytokine profile has been evaluated showing a significantly higher secretory rate of IL-8, IL-6 and chemokines MCP-1 and GM-CSF. We have also successfully induced human UDSCs into chondrogenic, osteogenic and myogenic cell lineages. Our findings indicate that UDSCs might have immense potential in the regeneration of the damaged tissues. Full article

(This article belongs to the Special Issue Biotechnology-Recent Advances)

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15 pages, 24833 KiB

Open AccessArticle

Controlled Transdermal Iontophoresis of Insulin from Water-Soluble Polypyrrole Nanoparticles: An In Vitro Study

by Kamran Tari, Soroush Khamoushian, Tayyebeh Madrakian, Abbas Afkhami, Marek Jan Łos, Arash Ghoorchian, Mohammad Reza Samarghandi and Saeid Ghavami

Int. J. Mol. Sci. 2021, 22(22), 12479; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212479 - 19 Nov 2021

Cited by 12 | Viewed by 2198

Abstract

The iontophoresis delivery of insulin (INS) remains a serious challenge due to the low permeability of the drug through the skin. This work aims to investigate the potential of water-soluble polypyrrole nanoparticles (WS-PPyNPs) as a drug donor matrix for controlled transdermal iontophoresis of INS. WS-PPyNPs have been prepared via a simple chemical polymerization in the presence of sodium dodecyl sulfate (SDS) as both dopant and the stabilizing agent. The synthesis of the soluble polymer was characterized using field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), fluorescence spectroscopy, and Fourier transform infrared (FT–IR) spectroscopy. The loading mechanism of INS onto the WS-PPyNPs is based on the fact that the drug molecules can be replaced with doped dodecyl sulfate. A two-compartment Franz-type diffusion cell was employed to study the effect of current density, formulation pH, INS concentration, and sodium chloride concentration on anodal iontophoresis (AIP) and cathodal iontophoresis (CIP) of INS across the rat skin. Both AIP and CIP delivery of INS using WS-PPyNPs were significantly increased compared to passive delivery. Furthermore, while the AIP experiment (60 min at 0.13 mA cm^–2) show low cumulative drug permeation for INS (about 20.48 µg cm⁻²); the CIP stimulation exhibited a cumulative drug permeation of 68.29 µg cm⁻². This improvement is due to the separation of positively charged WS-PPyNPs and negatively charged INS that has occurred in the presence of cathodal stimulation. The obtained results confirm the potential applicability of WS-PPyNPs as an effective approach in the development of controlled transdermal iontophoresis of INS. Full article

(This article belongs to the Special Issue Biotechnology-Recent Advances)

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24 pages, 4738 KiB

Open AccessArticle

Slow Off-Rate Modified Aptamer (SOMAmer) Proteomic Analysis of Patient-Derived Malignant Glioma Identifies Distinct Cellular Proteomes

by Thatchawan Thanasupawat, Aleksandra Glogowska, Christopher Pascoe, Sai Nivedita Krishnan, Maliha Munir, Farhana Begum, Jason Beiko, Jerry Krcek, Marc R. Del Bigio, Marshall Pitz, Yaoqing Shen, Victor Spicer, Kevin M. Coombs, John Wilkins, Sabine Hombach-Klonisch and Thomas Klonisch

Int. J. Mol. Sci. 2021, 22(17), 9566; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179566 - 03 Sep 2021

Cited by 6 | Viewed by 3136

Abstract

Malignant gliomas derive from brain glial cells and represent >75% of primary brain tumors. This includes anaplastic astrocytoma (grade III; AS), the most common and fatal glioblastoma multiforme (grade IV; GBM), and oligodendroglioma (ODG). We have generated patient-derived AS, GBM, and ODG cell models to study disease mechanisms and test patient-centered therapeutic strategies. We have used an aptamer-based high-throughput SOMAscan^® 1.3K assay to determine the proteomic profiles of 1307 different analytes. SOMAscan^® proteomes of AS and GBM self-organized into closely adjacent proteomes which were clearly distinct from ODG proteomes. GBM self-organized into four proteomic clusters of which SOMAscan^® cluster 4 proteome predicted a highly inter-connected proteomic network. Several up- and down-regulated proteins relevant to glioma were successfully validated in GBM cell isolates across different SOMAscan^® clusters and in corresponding GBM tissues. Slow off-rate modified aptamer proteomics is an attractive analytical tool for rapid proteomic stratification of different malignant gliomas and identified cluster-specific SOMAscan^® signatures and functionalities in patient GBM cells. Full article

(This article belongs to the Special Issue Biotechnology-Recent Advances)

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12 pages, 2366 KiB

Open AccessArticle

Functional Properties of Polyurethane Ureteral Stents with PLGA and Papaverine Hydrochloride Coating

by Magdalena Antonowicz, Janusz Szewczenko, Joanna Jaworska, Katarzyna Jelonek, Kamil Joszko, Bożena Gzik-Zroska, Paweł M. Nuckowski, Piotr Bryniarski, Zbigniew Paszenda, Damian S. Nakonieczny, Karla Čech Barabaszová and Janusz Kasperczyk

Int. J. Mol. Sci. 2021, 22(14), 7705; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147705 - 19 Jul 2021

Cited by 10 | Viewed by 5741

Abstract

Despite the obvious benefits of using ureteral stents to drain the ureters, there is also a risk of complications from 80–90%. The presence of a foreign body in the human body causes disturbances in its proper functioning. It can lead to biofilm formation on the stent surface, which may favor the development of urinary tract infections or the formation of encrustation, as well as stent fragmentation, complicating its subsequent removal. In this work, the effect of the polymeric coating containing the active substance-papaverine hydrochloride on the functional properties of ureteral stents significant for clinical practice were assessed. Methods: The most commonly clinically used polyurethane ureteral Double-J stent was selected for the study. Using the dip-coating method, the surface of the stent was coated with a poly(D,L-lactide-glycolide) (PLGA) coating containing the papaverine hydrochloride (PAP). In particular, strength properties, retention strength of the stent ends, dynamic frictional force, and the fluoroscopic visibility of the stent during X-ray imaging were determined. Results: The analysis of the test results indicates the usefulness of a biodegradable polymer coating containing the active substance for the modification of the surface of polyurethane ureteral stents. The stents coated with PLGA+PAP coating compared to polyurethane stents are characterized by more favorable strength properties, the smaller value of the dynamic frictional force, without reducing the fluoroscopic visibility. Full article

(This article belongs to the Special Issue Biotechnology-Recent Advances)

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Review

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15 pages, 1144 KiB

Open AccessReview

Integration of Genomic Profiling and Organoid Development in Precision Oncology

by Hyunho Yoon and Sanghoon Lee

Int. J. Mol. Sci. 2022, 23(1), 216; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010216 - 25 Dec 2021

Cited by 2 | Viewed by 3843

Abstract

Precision oncology involves an innovative personalized treatment strategy for each cancer patient that provides strategies and options for cancer treatment. Currently, personalized cancer medicine is primarily based on molecular matching. Next-generation sequencing and related technologies, such as single-cell whole-transcriptome sequencing, enable the accurate elucidation of the genetic landscape in individual cancer patients and consequently provide clinical benefits. Furthermore, advances in cancer organoid models that represent genetic variations and mutations in individual cancer patients have direct and important clinical implications in precision oncology. This review aimed to discuss recent advances, clinical potential, and limitations of genomic profiling and the use of organoids in breast and ovarian cancer. We also discuss the integration of genomic profiling and organoid models for applications in cancer precision medicine. Full article

(This article belongs to the Special Issue Biotechnology-Recent Advances)

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