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International Journal of Molecular... Jan 2024The cationic platinum(II) organometallic complex [Pt(terpy)Me] (terpy = 2,2':6',2″-terpyridine) at mild acidic pH interacts with poly(L-glutamic acid) (L-PGA) in its...
A Kinetic Investigation of the Supramolecular Chiral Self-Assembling Process of Cationic Organometallic (2,2':6',2″-terpyridine)methylplatinum(II) Complexes with Poly(L-glutamic Acid).
The cationic platinum(II) organometallic complex [Pt(terpy)Me] (terpy = 2,2':6',2″-terpyridine) at mild acidic pH interacts with poly(L-glutamic acid) (L-PGA) in its α-helix conformation, affording chiral supramolecular adducts. Their kinetics of formation have been investigated in detail as a function of the concentrations of both reagents and changing pH, ionic strength, the length of the polymeric scaffold and temperature. After a very fast early stage, the kinetic traces have been analyzed as three consecutive steps, suggesting a mechanism based on the electrostatic fast formation of a not-organized aggregate that subsequently evolves through different rearrangements to form the eventual supramolecular adduct. A model for this species has been proposed based on (i) the attractive electrostatic interaction of the cationic platinum(II) complexes and the polyelectrolyte and (ii) the π-stacking interactions acting among the [Pt(terpy)Me] units.
Topics: Glutamic Acid; Platinum; Poly A; Cations; Kinetics
PubMed: 38256248
DOI: 10.3390/ijms25021176 -
International Journal of Molecular... Jan 2024Polymer nanocomposites filled with carbon nanoparticles (CNPs) are a hot topic in materials science. This article discusses the current research on the use of these...
Polymer nanocomposites filled with carbon nanoparticles (CNPs) are a hot topic in materials science. This article discusses the current research on the use of these materials as interfacial electron transfer films for solid contact potentiometric membrane sensors (SC-PMSs). The results of a comparative study of plasticized poly (vinyl chloride) (pPVC) matrices modified with single-walled carbon nanotubes (SWCNTs), fullerenes-C60, and their hybrid ensemble (SWCNTs-C60) are reported. The morphological characteristics and electrical conductivity of the prepared nanostructured composite films are reported. It was found that the specific electrical conductivity of the pPVC/SWCNTs-C60 polymer film was higher than that of pPVC filled with individual nanocomponents. The effectiveness of this composite material as an electron transfer film in a new potentiometric membrane sensor for detecting phenylpyruvic acid (in anionic form) was demonstrated. Screening for this metabolic product of phenylalanine in body fluids is of significant diagnostic interest in phenylketonuria (dementia), viral hepatitis, and alcoholism. The developed sensor showed a stable and fast Nernstian response for phenylpyruvate ions in aqueous solutions over the wide linear concentration range of 5 × 10-1 × 10 M, with a detection limit of 10 M.
Topics: Nanotubes, Carbon; Vinyl Chloride; Membranes; Nanocomposites; Poly A; Polymers; Phenylpyruvic Acids
PubMed: 38256194
DOI: 10.3390/ijms25021124 -
International Journal of Molecular... Jan 2024In this study, a novel film of poly(vinyl alcohol) (PVA)/pullulan (PULL) with improved surface characteristics was prepared from poly(vinyl acetate) (PVAc)/PULL blend...
In this study, a novel film of poly(vinyl alcohol) (PVA)/pullulan (PULL) with improved surface characteristics was prepared from poly(vinyl acetate) (PVAc)/PULL blend films with various mass ratios after the saponification treatment in a heterogeneous medium. According to proton nuclear magnetic resonance (H-NMR), Fourier transform infrared, and X-ray diffraction results, it was established that the successful fabrication of saponified PVA/PULL (100/0, 90/10, and 80/20) films could be obtained from PVAc/PULL (100/0, 90/10, and 80/20) films, respectively, after 72 h saponification at 50 °C. The degree of saponification calculated from H-NMR analysis results showed that fully saponified PVA was obtained from all studied films. Improved hydrophilic characteristics of the saponified films were revealed by a water contact angle test. Moreover, the saponified films showed improved mechanical behavior, and the micrographs of saponified films showed higher surface roughness than the unsaponified films. This kind of saponified film can be widely used for biomedical applications. Moreover, the reported saponified film dressing extended the lifespan of dressing as determined by its self-healing capacity and considerably advanced in vivo wound-healing development, which was attributed to its multifunctional characteristics, meaning that saponified film dressings are promising candidates for full-thickness skin wound healing.
Topics: Polyvinyl Alcohol; Ethanol; Glucans; Bandages; Poly A; Polyvinyl Chloride
PubMed: 38256100
DOI: 10.3390/ijms25021026 -
Cancer Letters Mar 2024Novel biomarkers and therapeutic strategies for prostate-cancer (PCa) are required to overcome its lethal progression. The dysregulation/implication of the...
Novel biomarkers and therapeutic strategies for prostate-cancer (PCa) are required to overcome its lethal progression. The dysregulation/implication of the RNA-Exosome-complex (REC; cellular machinery controlling the 3'-5'processing/degradation of most RNAs) in different cancer-types, including PCa, is poorly known. Herein, different cellular/molecular/preclinical approaches with human PCa-samples (tissues and/or plasma of 7 independent cohorts), and in-vitro/in-vivo PCa-models were used to comprehensively characterize the REC-profile and explore its role in PCa. Moreover, isoginkgetin (REC-inhibitor) effects were evaluated on PCa-cells. We demonstrated a specific dysregulation of the REC-components in PCa-tissues, identifying the Poly(A)-Binding-Protein-Nuclear 1 (PABPN1) factor as a critical regulator of major cancer hallmarks. PABPN1 is consistently overexpressed in different human PCa-cohorts and associated with poor-progression, invasion and metastasis. PABPN1 silencing decreased relevant cancer hallmarks in multiple PCa-models (proliferation/migration/tumourspheres/colonies, etc.) through the modulation of key cancer-related lncRNAs (PCA3/FALEC/DLEU2) and mRNAs (CDK2/CDK6/CDKN1A). Plasma PABPN1 levels were altered in patients with metastatic and tumour-relapse. Finally, pharmacological inhibition of REC-activity drastically inhibited PCa-cell aggressiveness. Altogether, the REC is drastically dysregulated in PCa, wherein this novel molecular event/mechanism, especially PABPN1 alteration, may be potentially exploited as a novel prognostic and therapeutic tool for PCa.
Topics: Male; Humans; Exosome Multienzyme Ribonuclease Complex; Exosomes; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Neoplasm Recurrence, Local; Prostatic Neoplasms; RNA, Messenger; Poly(A)-Binding Protein I
PubMed: 38244911
DOI: 10.1016/j.canlet.2023.216604 -
Pathology, Research and Practice Feb 2024Epithelial-mesenchymal transition (EMT), angiogenesis, cell adhesion and extracellular matrix (ECM) interaction are essential for colorectal cancer (CRC) metastasis. Low...
Epithelial-mesenchymal transition (EMT), angiogenesis, cell adhesion and extracellular matrix (ECM) interaction are essential for colorectal cancer (CRC) metastasis. Low grade mucinous neoplasia of the appendix (LAMN) and its advanced state low grade pseudomyxoma peritonei (lgPMP) show local aggressiveness with very limited metastatic potential as opposed to CRC. To better understand the underlying processes that foster or impede metastatic spread, we compared LAMN, lgPMP, and CRC with respect to their molecular profile with subsequent pathway analysis. LAMN, lgPMP and (mucinous) CRC cases were subjected to transcriptomic analysis utilizing Poly(A) RNA sequencing. Successfully sequenced cases (LAMN n = 10, 77%, lgPMP n = 13, 100% and CRC n = 8, 100%) were investigated using bioinformatic and statistical tests (differential expression analysis, hierarchical clustering, principal component analysis and gene set enrichment analysis). We identified a gene signature of 28 genes distinguishing LAMN, lgPMP and CRC neoplasias. Ontology analyses revealed that multiple pathways including EMT, ECM interaction and angiogenesis are differentially regulated. Fifty-three significantly differentially regulated gene sets were identified between lgPMP and CRC followed by CRC vs. LAMN (n = 21) and lgPMP vs. LAMN (n = 16). Unexpectedly, a substantial enrichment of the EMT gene set was observed in lgPMP vs. LAMN (FDR=0.011) and CRC (FDR=0.004). Typical EMT markers were significantly upregulated (Vimentin, TWIST1, N-Cadherin) or downregulated (E-Cadherin) in lgPMP. However, MMP1 and MMP3 levels, associated with EMT, ECM and metastasis, were considerably higher in CRC. We show that the different tumor biological behaviour and metastatic spread pattern of midgut malignancies is reflected in a different gene expression profile. We revealed a strong activation of the EMT program in non-metastasizing lgPMP vs. CRC. Hence, although EMT is considered a key step in hematogenous spread, successful EMT does not necessarily lead to hematogenous dissemination. This emphasizes the need for further pathway analyses and forms the basis for mechanistic and therapy-targeting research.
Topics: Humans; Pseudomyxoma Peritonei; Transcriptome; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Peritoneal Neoplasms; Gene Expression Profiling; Cell Line, Tumor; Cell Movement
PubMed: 38232629
DOI: 10.1016/j.prp.2024.155129 -
International Journal of Molecular... Dec 2023Undifferentiated germ cells, including the spermatogonial stem cell subpopulation required for fertility restoration using human immature testicular tissue (ITT), are...
Optimized Recovery of Immature Germ Cells after Prepubertal Testicular Tissue Digestion and Multi-Step Differential Plating: A Step towards Fertility Restoration with Cancer-Cell-Contaminated Tissue.
Undifferentiated germ cells, including the spermatogonial stem cell subpopulation required for fertility restoration using human immature testicular tissue (ITT), are difficult to recover as they do not easily adhere to plastics. Due to the scarcity of human ITT for research, we used neonatal porcine ITT. Strategies for maximizing germ cell recovery, including a comparison of two enzymatic digestion protocols (P1 and P2) of ITT fragment sizes (4 mm and 8 mm and multi-step differential plating were explored. Cellular viability and yield, as well as numbers and proportions of DDX4+ germ cells, were assessed before incubating the cell suspensions overnight on uncoated plastics. Adherent cells were processed for immunocytochemistry (ICC) and floating cells were further incubated for three days on Poly-D-Lysine-coated plastics. Germ cell yield and cell types using ICC for SOX9, DDX4, ACTA2 and CYP19A1 were assessed at each step of the multi-step differential plating. Directly after digestion, cell suspensions contained >92% viable cells and 4.51% DDX4+ germ cells. Pooled results for fragment sizes revealed that the majority of DDX4+ cells adhere to uncoated plastics (P1; 82.36% vs. P2; 58.24%). Further incubation on Poly-D-Lysine-coated plastics increased germ cell recovery (4.80 ± 11.32 vs. 1.90 ± 2.07 DDX4+ germ cells/mm, respectively for P1 and P2). The total proportion of DDX4+ germ cells after the complete multi-step differential plating was 3.12%. These results highlight a reduced proportion and number of germ cells lost when compared to data reported with other methods, suggesting that multi-step differential plating should be considered for optimization of immature germ cell recovery. While Poly-D-Lysine-coating increased the proportions of recovered germ cells by 16.18% (P1) and 28.98% (P2), future studies should now focus on less cell stress-inducing enzymatic digestion protocols to maximize the chances of fertility restoration with low amounts of cryo-banked human ITT.
Topics: Humans; Animals; Swine; Neoplasms; Germ Cells; Fertility; Lysine; Plastics; Poly A; Digestion; Polylysine
PubMed: 38203691
DOI: 10.3390/ijms25010521 -
International Journal of Molecular... Dec 2023Delivery systems for biologically active substances such as proanthocyanidins (PCANs), produced in the form of electrospun nonwoven through the electrospinning method,...
Delivery systems for biologically active substances such as proanthocyanidins (PCANs), produced in the form of electrospun nonwoven through the electrospinning method, were designed using a polymeric blend of poly(L-lactide-co-glycolide) (PLGA)and poly[(R,S)-3-hydroxybutyrate] ((R,S)-PHB). The studies involved the structural and thermal characteristics of the developed electrospun three-dimensional fibre matrices unloaded and loaded with PCANs. In the next step, the hydrolytic degradation tests of these systems were performed. The release profile of PCANs from the electrospun nonwoven was determined with the aid of UV-VIS spectroscopy. Approximately 30% of the PCANs were released from the tested electrospun nonwoven during the initial 15-20 days of incubation. The chemical structure of water-soluble oligomers that were formed after the hydrolytic degradation of the developed delivery system was identified through electrospray ionization mass spectrometry. Oligomers of lactic acid and OLAGA oligocopolyester, as well as oligo-3-hydroxybutyrate terminated with hydroxyl and carboxyl end groups, were recognized as degradation products released into the water during the incubation time. It was also demonstrated that variations in the degradation rate of individual mat components influenced the degradation pattern and the number of formed oligomers. The obtained results suggest that the incorporation of proanthocyanidins into the system slowed down the hydrolytic degradation process of the poly(L-lactide--glycolide)/poly[(R,S)-3-hydroxybutyrate] three-dimensional fibre matrix. In addition, in vitro cytotoxicity and antimicrobial studies advocate the use of PCANs for biomedical applications with promising antimicrobial activity.
Topics: Humans; Polyesters; Periodontal Pocket; 3-Hydroxybutyric Acid; Proanthocyanidins; Drug Delivery Systems; Anti-Infective Agents; Hydroxybutyrates; Poly A; Water
PubMed: 38203673
DOI: 10.3390/ijms25010503 -
International Journal of Molecular... Dec 2023Poly(butylene sebacate-co-terephthalate) (PBSeT) copolyesters are prepared by melt polymerization via two-step transesterification and polycondensation using...
Poly(butylene sebacate-co-terephthalate) (PBSeT) copolyesters are prepared by melt polymerization via two-step transesterification and polycondensation using pentaerythritol (PE) as a branching agent. The effects of the incorporated PE on its chemical, thermal, mechanical, and degradation properties, along with the rheological properties of its melt, are investigated. The highest molecular weight and intrinsic viscosity along with the lowest melt flow index were achieved at a PE content of 0.2 mol%, with minimal reduction in the tensile strength and the highest tear strength. The addition of PE did not significantly influence the thermal behavior and stability of the PBSeT copolyesters; however, the elongation at break decreased with increasing PE content. The sample with 0.2 mol% PE exhibited a higher storage modulus and loss modulus as well as a lower loss angle tangent than the other samples, indicating improved melt elasticity. The incorporation of more than 0.2 mol% PE enhanced the enzymatic degradation of copolyesters. In summary, including within 0.2 mol%, PE effectively improved both the processability-related characteristics and degradation properties of PBSeT copolyesters, suggesting their potential suitability for use in agricultural and packaging materials.
Topics: Poly A; Esterification; Fatty Acids; Propylene Glycols; Phthalic Acids; Alkenes
PubMed: 38203226
DOI: 10.3390/ijms25010055 -
Cells Dec 2023Small ubiquitin-related modifiers (SUMOs) function as post-translational protein modifications and regulate nearly every aspect of cellular function. While a single... (Review)
Review
Small ubiquitin-related modifiers (SUMOs) function as post-translational protein modifications and regulate nearly every aspect of cellular function. While a single ubiquitin protein is expressed across eukaryotic organisms, multiple SUMO paralogues with distinct biomolecular properties have been identified in plants and vertebrates. Five SUMO paralogues have been characterized in humans, with SUMO1, SUMO2 and SUMO3 being the best studied. SUMO2 and SUMO3 share 97% protein sequence homology (and are thus referred to as SUMO2/3) but only 47% homology with SUMO1. To date, thousands of putative sumoylation substrates have been identified thanks to advanced proteomic techniques, but the identification of SUMO1- and SUMO2/3-specific modifications and their unique functions in physiology and pathology are not well understood. The SUMO2/3 paralogues play an important role in proteostasis, converging with ubiquitylation to mediate protein degradation. This function is achieved primarily through SUMO-targeted ubiquitin ligases (STUbLs), which preferentially bind and ubiquitylate poly-SUMO2/3 modified proteins. Effects of the SUMO1 paralogue on protein solubility and aggregation independent of STUbLs and proteasomal degradation have also been reported. Consistent with these functions, sumoylation is implicated in multiple human diseases associated with disturbed proteostasis, and a broad range of pathogenic proteins have been identified as SUMO1 and SUMO2/3 substrates. A better understanding of paralogue-specific functions of SUMO1 and SUMO2/3 in cellular protein quality control may therefore provide novel insights into disease pathogenesis and therapeutic innovation. This review summarizes current understandings of the roles of sumoylation in protein quality control and associated diseases, with a focus on the specific effects of SUMO1 and SUMO2/3 paralogues.
Topics: Humans; Animals; Proteomics; Ubiquitin; Protein Processing, Post-Translational; Eukaryota; Poly A; Small Ubiquitin-Related Modifier Proteins; SUMO-1 Protein
PubMed: 38201212
DOI: 10.3390/cells13010008 -
G3 (Bethesda, Md.) Mar 2024The decay of messenger RNA with a premature termination codon by nonsense-mediated decay (NMD) is an important regulatory pathway for eukaryotes and an essential pathway...
The decay of messenger RNA with a premature termination codon by nonsense-mediated decay (NMD) is an important regulatory pathway for eukaryotes and an essential pathway in mammals. NMD is typically triggered by the ribosome terminating at a stop codon that is aberrantly distant from the poly-A tail. Here, we use a fluorescence screen to identify factors involved in NMD in Saccharomyces cerevisiae. In addition to the known NMD factors, including the entire UPF family (UPF1, UPF2, and UPF3), as well as NMD4 and EBS1, we identify factors known to function in posttermination recycling and characterize their contribution to NMD. These observations in S. cerevisiae expand on data in mammals indicating that the 60S recycling factor ABCE1 is important for NMD by showing that perturbations in factors implicated in 40S recycling also correlate with a loss of NMD.
Topics: Animals; Saccharomyces cerevisiae; RNA Helicases; Nonsense Mediated mRNA Decay; Ribosomes; RNA, Messenger; Mammals
PubMed: 38198768
DOI: 10.1093/g3journal/jkad295