We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: (1) primary sulfonamide group recognizing carbonic anhydrases (CA), (2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and (3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification.
View Article and Find Full Text PDFIntroduction: Although morphological and anatomical studies indicate that venous wall weakening and subendothelial fibrosis characterize varicose veins (VV), the pathogenesis of VV remains poorly understood. The aim of this study is to obtain protein expression profiles in patients with VV and thereby get a step closer to understanding the pathogenesis of VV.
Methods: Specimens were obtained from total of 10 patients, that is, from 5 patients undergoing VV surgical stripping and from 5 non-VV patients undergoing bypass surgery.
A high temperature-adapted bacteriophage, vB_PtoS_NIIg3.2 (NIIg3.2), was isolated in Lithuania from compost heaps using strain NIIg-3 as a host for phage propagation.
View Article and Find Full Text PDFNon-canonical 5'-caps removing RNA hydrolase NudC, along with stress-responsive RNA helicase CsdA, is crucial for 5'-NAD-RNA decapping and bacterial movement.
View Article and Find Full Text PDFWe report a detailed characterization of five thermophilic bacteriophages (phages) that were isolated from compost heaps in Vilnius, Lithuania using strains as the hosts for phage propagation. The efficiency of plating experiments revealed that phages formed plaques from 45 to 80 °C. Furthermore, most of the phages formed plaques surrounded by halo zones, indicating the presence of phage-encoded bacterial exopolysaccharide (EPS)-degrading depolymerases.
View Article and Find Full Text PDFThe prevalence of infertility is getting higher over the years. The increasing age of first-time parents, although economically more desirable, can cause various biological problems from low natural conception rate to poor pregnancy outcomes. The growing demand for assisted reproductive technology procedures worldwide draws medical specialists' and scientists' attention to various elements which could lead to successful conception, such as follicular fluid (FF) and hormones.
View Article and Find Full Text PDFLytic viruses of bacteria (bacteriophages, phages) are intracellular parasites that take over hosts' biosynthetic processes for their propagation. Most of the knowledge on the host hijacking mechanisms has come from the studies of the lytic phage T4, which infects . The integrity of T4 development is achieved by strict control over the host and phage processes and by adjusting them to the changing infection conditions.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) is an aggressive, heterogeneous group of malignancies with different clinical behaviors and different responses to therapy. For many types of cancer, finding cancer early makes it easier to treat. Identifying prognostic molecular markers and understanding their biology are the first steps toward developing novel diagnostic tools or therapies for patients with AML.
View Article and Find Full Text PDFFluorophores with multifunctional properties known as rare-earth-doped nanoparticles (RENPs) are promising candidates for bioimaging, therapy, and drug delivery. When applied , these nanoparticles (NPs) have to retain long blood-circulation time, bypass elimination by phagocytic cells, and successfully arrive at the target area. Usually, NPs in a biological medium are exposed to proteins, which form the so-called "protein corona" (PC) around the NPs and influence their targeted delivery and accumulation in cells and tissues.
View Article and Find Full Text PDFSurvival rates from pancreatic cancer have remained stagnant for decades due to the heterogenic nature of the disease. This study aimed to find a new advanced biomarker and evaluate its clinical capabilities, thus enabling more individualised pancreatic cancer management. Between 2013 and 2020, 267 patients were included in the study.
View Article and Find Full Text PDFWhen looking for the causes and treatments of infertility, much attention is paid to one of the reproductive tissues-the endometrium. Therefore, endometrial stem cells are an attractive target for infertility studies in women of unexplained origin. Menstrual blood stem cells (MenSCs) are morphologically and functionally similar to cells derived directly from the endometrium; with dual expression of mesenchymal and embryonic cell markers, they proliferate and regenerate better than bone marrow mesenchymal stem cells.
View Article and Find Full Text PDFRab40b is a SOCS box-containing protein that regulates the secretion of MMPs to facilitate extracellular matrix remodeling during cell migration. Here, we show that Rab40b interacts with Cullin5 via the Rab40b SOCS domain. We demonstrate that loss of Rab40b-Cullin5 binding decreases cell motility and invasive potential and show that defective cell migration and invasion stem from alteration to the actin cytoskeleton, leading to decreased invadopodia formation, decreased actin dynamics at the leading edge, and an increase in stress fibers.
View Article and Find Full Text PDFA cold-adapted siphovirus, vB_PagS_AAS23 (AAS23) was isolated in Lithuania using the strain AUR for the phage propagation. The double-stranded DNA genome of AAS23 (51,170 bp) contains 92 probable protein encoding genes, and no genes for tRNA. A comparative sequence analysis revealed that 25 of all AAS23 open reading frames (ORFs) code for unique proteins that have no reliable identity to database entries.
View Article and Find Full Text PDFBackground/aim: Pancreatic ductal adenocarcinoma is one of the deadliest forms of human cancer. Since only a vast panel of cell lines can fully recapitulate disease heterogeneity, our aim was to establish a new pancreatic cancer cell line.
Materials And Methods: Newly established pancreatic ductal adenocarcinoma cell line Capan-26 was characterized by assessing growth rate, tumor and stem cell marker expression, colony forming efficiency, mutations of KRAS and TP53 genes, karyotype and sensitivity to drug treatment.
spp. are ubiquitous in nature and are increasingly being recognized as emerging nosocomial pathogens. Nevertheless, to date, only 30 complete genome sequences of phages are available in GenBank, and nearly all of those phages were isolated on .
View Article and Find Full Text PDFA novel cold-adapted siphovirus, vB_PagS_AAS21 (AAS21), was isolated in Lithuania using as the host for phage propagation. AAS21 has an isometric head (~85 nm in diameter) and a non-contractile flexible tail (~174 × 10 nm). With a genome size of 116,649 bp, bacteriophage AAS21 is the largest -infecting siphovirus sequenced to date.
View Article and Find Full Text PDFHuman activating signal cointegrator homology (ASCH) domain-containing proteins are widespread and diverse but, at present, the vast majority of those proteins have no function assigned to them. This study demonstrates that the 103-amino acid Escherichia coli protein YqfB, previously identified as hypothetical, is a unique ASCH domain-containing amidohydrolase responsible for the catabolism of N-acetylcytidine (ac4C). YqfB has several interesting and unique features: i) it is the smallest monomeric amidohydrolase described to date, ii) it is active towards structurally different N-acylated cytosines/cytidines, and iii) it has a high specificity for these substrates (k/K up to 2.
View Article and Find Full Text PDFAlthough treatment of colorectal cancer with 5-florouracil and oxaliplatin is widely used, it is frequently followed by a relapse. Therefore, there is an urgent need for profound understanding of chemotherapy resistance mechanisms as well as the profiling of predictive markers for individualized treatment. In this study, we identified the changes in 14 miRNAs in 5-fluouracil and 40 miRNAs in oxaliplatin-resistant cell lines by miRNA sequencing.
View Article and Find Full Text PDFHybrid organometallic polymers are a class of functional materials which can be used to produce structures with sub-micron features via laser two-photon polymerisation. Previous studies demonstrated the relative biocompatibility of Al and Zr containing hybrid organometallic polymers in vitro. However, a deeper understanding of their effects on intracellular processes is needed if a tissue engineering strategy based on these materials is to be envisioned.
View Article and Find Full Text PDF: Nitric oxide (NO) is known to exert cardioprotective effects against heart ischemic damage and may be involved in ischemic pre- and postconditioning. NO-triggered cardioprotective mechanisms are not well understood but may involve regulation of mitochondrial permeability transition pore (mPTP). In this study, we aimed to identify differentially phosphorylated mitochondrial proteins possibly involved in the NO/protein kinase G (PKG)/mPTP signaling pathway that can increase the resistance of cardiomyocytes to ischemic damage.
View Article and Find Full Text PDFBacteriocins are ribosomally synthesized peptides/proteins produced by bacteria. These compounds have antibacterial activity against other bacteria that are usually closely related to the producer strain. Here we describe bacteriocin geobacillin 26 from a thermophilic Gram-positive bacterium Geobacillus stearothermophilus 15.
View Article and Find Full Text PDFTreatment of acute myeloid leukemia (AML) is still a challenge because of common relapses or resistance to treatment. Therefore, the development of new therapeutic approaches is necessary. Various studies have shown that certain cancers, including some chemoresistant AML subsets, have upregulated oxidative phosphorylation.
View Article and Find Full Text PDFAntitumor drug resistance remains a major challenge in cancer chemotherapy. Here we investigated the mechanism of acquired resistance to a novel anticancer agent RH1 designed to be activated in cancer cells by the NQO1 enzyme. Data show that in some cancer cells RH1 may act in an NQO1-independent way.
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