Biopolym. Cell is an open access peer-reviewed international journal that publishes original contributions in molecular biology and related areas: Structure and function of biopolymers in different cells at different conditions; Genome regulation; Molecular mechanisms of differentiation; Oncogenesis; Cell-virus interaction; Biotechnology; Bioorganic chemistry; Drug design; Biology of peptides, nucleoside derivatives and modified oligonucleotides
Institute of Molecular Biology and Genetics of the NAS of Ukraine.
Modified method for analysis of InDel ACE1 gene polymorphism using the temperature melting curves of PCR products
Aim. The ACE1 gene is a key to the renin–angiotensin system, as it encode the ACE1 enzyme, which regulates blood pressure and water–electrolyte balance. The InDel (I/D) polymorphism of the ACE1 gene causes a different level of enzyme synthesis and is associated with various pathological conditions, including the course of COVID–19. The aim of our study was to develop an efficient method for the analysis of I/D polymorphism of the ACE1 gene by analyzing the melting temperature curves of specific PCR products. Methods. Genotyping was carried out by the PCR method using DNA isolated from peripheral blood leukocytes. The primers were designed using BLAST SEARCH and synthesized at METABION (Germany). The reaction was carried out using the "HOT FIREPol EvaGreen qPCR Mix Plus" mixture. Amplification was performed on iQ5TM Multicolor Real–Time PCR Detection System (BIO–RAD), melting curves were analyzed using BIO–RAD iQ5 Optical System Software V 2.0. Results. The proposed method, using one pair of primers, turned out to be effective for detecting genotypes based on the melting temperature curves of PCR products: the peak at 83–85°C corresponded to deletion, at 86–89°C to insertion, and in the presence of both peaks, the genotype was defined as heterozygous. Conclusions. The proposed method of genotyping the I/D polymorphism of the ACE1 gene is simple and reliable, and can be used for the analysis of genetic markers of cardiovascular pathology and the prognosis of the course of COVID–19.
Cytotoxic Effect of Endothelial-Monocyte Activating Polypeptide II on Glioma Cells in vitro
Aim. To investigate the in vitro cytotoxic effect of EMAP II on glioma cells by determining the viability of cell culture using the MTT test. Methods. The culture of the human glioma cell line U251MG and the primary cell culture obtained from the malignant glioma tissue fragments after surgical intervention were treated with EMAP II at different concentrations. Cell viability was determined by MTT assay. Results. Cytokine EMAP II exhibits dose–dependent cytotoxic properties in the U251GM cell culture. In the studied concentration range (1.024 nM – 10.0 μM), it exhibits in the MTT test a biphasic effect on cell survival with two statistically significant minima in the concentration range of 640.0 pM (71.6 ± 6.4 %) and 10.0 μM (49.2 ± 11.4 %). The obtained results may indicate that EMAP II can interact with its receptors at ultralow concentrations in a different way than at high concentrations. A dose–dependent cytotoxic effect of EMAP II on glioma cells in the primary culture was shown as well but in the glioblastoma cells this dependence was less pronounced than in the gliomas grade 3 of anaplasia ones. It may be connected with both individual features of patients and genetic differences between glioblastoma and diffuse gliomas grade 3 of anaplasia cells. Conclusions. The complex pattern of dose dependent action of EMAP II on glioma cells may be a result of the multifunctionality of this polypeptide and its ability to interact with various target receptors.
The IAP Inhibitor GDC-0152 Suppresses Cell Proliferation and Induces Apoptosis in Colon Cancer Cell Lines
Aim. The present study was aimed to explore the impact of inhibitor of apoptosis protein (IAP) small molecule inhibitor GDC-0152 on colon cancer cells (HCT-116 and HT-29). Methods. The effects of GDC-0152 on colon cancer cells, cell viability, and proliferation were assessed using WST-1 assay and Real Time Cell Analysis System (xCELLigence), while apoptosis was detected using AO/EBr staining and Annexin V/Flow cytometry assays. The expression of XIAP were analyzed using western blotting analysis. Results. It was shown that GDC-0152 can inhibit the proliferation and clonogenic potential of colon cancer cells. We used a viability assay to demonstrate that GDC-0152 inhibited cell growth with IC50 values 28,90 μM in HCT-116, and 24,32 μM in HT-29. A wound healing assay showed that GDC-0152 inhibited migration of colon cancer cells. Further validation found that GDC-0152 induced apoptosis in colon cancer cells. Conclusions. Taken together, our results suggest that GDC-0152 suppressed the CC cell proliferation, migration, and induces apoptosis in a concentration-dependent manner. In conclusion, GDC-0152, a IAP inhibitor, can be considered as a valid approach to target cell death in colon cancer.
Monitoring and phylogenetic analysis of Cucumber mosaic virus isolates from Cucurbitaceae plants in Ukraine
Aim. To conduct monitoring and phylogenetic analysis of the cucumber mosaic virus isolates from agrocenoses of Ukraine. Methods. Enzyme-linked immunosorbent assay, RT-PCR, sequencing and phylogenetic analysis. Results. The agrocenoses of different regions of Ukraine were examined and the plants of Cucurbitaceae with the manifestations of viral diseases were selected. Using an enzyme-linked immunosorbent assay, 131 samples of Cucurbitaceae plants were tested and the antigens of cucumber mosaic virus (CMV) were detected. The RT-PCR resulted in amplification products of 500 bp in size, which corresponds to the sequence of the capsid protein gene of CMV. Based on the sequence data, a phylogenetic tree of the selected CMV isolates was constructed. Conclusions. It was found that Ukrainian isolates of CMV obtained from the plants of Cucurbitaceae are represented only in the cluster of group I of subgroups IA and IB.The most related to the Ukrainian isolates were strains T35 and T19 (China), strain I17F (France) and banana (Israel).
Genomics, Transcriptomics and Proteomics
ZFP36 expression profiles in breast tumors of different stages and hormonal receptor status
Aim. in current study we investigated how ZFP36 expression varies in breast cancer tumors of different histological types, grades, metastatic status, as well as in tumors with different progesterone and human EGFR receptor 2 (HER2) status to assess its use as a potential breast cancer biomarker. Methods. RT-qPCR. Results. we show that ZFP36 expression is elevated in T1-2 and N0-N1 tumors compared to adjacent tissues and T3-4 and N2 tumors, respectively. We also show that ZFP36 expression does not vary in samples with different PR status, but significantly increases with HER2 amplification. Conclusions. ZFP36 is a promising candidate to the HER2-enriched breast cancer biomarker, although further studies are necessary for verification.
Interaction of 5’–ribonucleoside monophosphates with Interferon α–2b
Aim. To characterize by different approaches the interaction of interferon α–2b (IFN α–2b) with cytidine 5’–monophophosphoric acid (5’–CMP), guanosine 5’–monophophosphoric acid (5’–GMP), uridine 5’– monophophosphoric acid (5’–UMP) and their disodium salts, in the presence and absence of D–mannitol. Methods. Spectroscopy (time–resolved, circular dichroism and fluorescence), isothermal nanocalorimetry. Results. Using IFN α–2b intrinsic fluorescence measurements we established that 5’–GMP and 5’–CMP interact with IFN α–2b stronger than their disodium salts while no difference of affinity was observed for 5’–UMP and its disodium salt. The presence of D–mannitol enhances the observed effects for 5’–GMP and 5’–CMP, but not for their disodium salts and all forms of 5’–UMP. Thermodynamic measurements reveal that the interaction of all tested 5’–ribonucleoside monophosphoric acids with IFN α–2b is exothermic, while of all disodium salt of 5’–ribonucleoside monophosphates is endothermic. The entropy factor TΔS was calculated to be negative in the presence of all 5’–ribonucleoside monophosphoric acids indicating a decrease of randomness in the system and positive in the presence of their disodium salts indicating an opposite effect. Circular dichroism measurements showed that 5’–ribonucleoside monophosphoric acids induce a decrease of the regular alpha helices content and increase the unstructured regions length in INF α–2b. In contrast, their disodium salts make rather stabilizing effect on the secondary structure elements of the protein. Conclusions. 5’–ribonucleoside monophosphoric acids used in this study interact with IFN α–2b in different way compared to their disodium salts. Acid forms of 5’–ribonucleoside monophosphates possess higher affinity to IFN α–2b and destabilize secondary structure elements of this protein. This may restrain a conformational mobility of IFN α–2b and as a consequence modify its functional activity. In contrast, disodium salts of 5’–ribonucleoside monophosphates display a weak affinity to IFN α–2b and stabilize its secondary structure organization.
Tyrosine kinase ABL1 as a promising molecular target for anticancer drugs 17
Tyrosine kinase ABL1 plays an important role in many key cellular processes linked to growth, proliferation, differentiation, survival, apoptosis, cell motility, adhesion, etc. However, this protein kinase is also associated with the development of several oncological diseases. In this review we summarize the literature data on the ABL1 structure, function, the role in cancer and known inhibitors of the kinase.
Evaluation of phytochemical, antioxidative and antibacterial activities in Hypericum perforatum L. callus cultures
Aim. Hypericum perforatum L. and Gingko biloba L. are two examples of top-selling plants that have been cultivated by European and American phytopharmaceutical companies for many years [1]. Medicinal plant biotechnology could enhance the formation and accumulation of desirable natural products and develop new and effective pharmaceuticals. Hypericum perforatum L. extracts accumulate phytochemicals such as flavonoids, biflavones, phenolic acids, naphthodiantrone derivatives, and phloroglucinols. These extracts are known to have antidepressant, antidiabetic, antioxidant, antibacterial, antiviral, and anticancer activities [2]. The main aim of the present study was to investigate the antioxidant and antibacterial activities of Hypericum perforatum L. phytochemicals in callus culture extracts. Conclusions. The results suggest that the addition of the phytohormones TDZ (0.5 mg/L) and IAA (0.1 mg/L) to the MS medium is a suitable method to promote the formation of bioactive secondary metabolites in Hypericum perforatum L. callus cultures.
Natural alkaloids noncovalently bound to C60 fullerene are potent anticancer phytotherapeutic agents
Aim. Conventional anticancer drugs have a number of known limitations but the development of new ones takes a long time, requires significant funding, and has a low success rate. Repurposing of pharmacologically active plant alkaloids Berberine (Ber) and Piperlongumine (Pl) and finding nanoplatforms for their delivery to cancer cells seems promising to be addressed. The ability of the C60 fullerene (C60) carbon nanostructure to be functionalized with therapeutic agents makes it a potential drug carrier. The aim of this study was to prove a non-covalent functionalization of C60 with Ber or PL and to check the effectiveness of these nanocomplexes against Lewis lung carcinoma (LLC) both in vitro and in vivo. Conclusions. The proposed nanocomplexes of alkaloids with C60 represent promising drugs for the treatment of metastatic lung cancer.
Novel non-nucleoside MGMT inhibitors: potential in combined alkylating chemotherapy
Aim. O6-methylguanine-DNA methyltransferase (MGMT) is an inducible repair enzyme that removes alkyl residues from DNA, thereby reducing the effectiveness of alkylating chemotherapy. Therefore, the MGMT inhibitors are used in medical practice. However, the most common of them, O6-benzylguanine and its analogs, have proven to be toxic to hematopoietic cells. That is why the search for new alternative inhibitors is essential. Conclusions. The new low molecular weight non-nucleoside MGMT inhibitors effectively reduce MGMT protein levels and enhance the cytotoxic effects of MNNG across different cancer cell lines. In T98G cells, the combination treatment increases autophagy and makes cells more sensitive to MNNG. The in vivo study confirms the therapeutic potential of these inhibitors, with significant tumor reduction or remission observed. Inhibitor 41B demonstrated the greatest overall efficacy, making it a promising candidate for further development in the combined alkylating chemotherapy.
Smart biomaterials based on Laponite®: acute toxicity and influence on the redox state and enzyme activity in the organs of the detoxification system of mice
Aim. The work aims to prepare smart biomaterials (thermosensitive Poly(N-isopropylacrylamide)-based hydrogels cross-linked by acid-activated Lap (aLap) doped with doxorubicin (Dox) (aLap+Dox/hydrogel)), to determine and compare the indicators of its acute toxicity, and to estimate its effects on the level of generation of superoxide radicals (SR), activity of ribonucleases (RNases), ornithine decarboxylase (ODC) and gelatinase (matrix metalloproteinases-2 and -9 (MMP-2 and -9)) in liver and kidney tissues of C57Bl/6 mice. Conclusions. Dox in aLap-based/hydrogels exhibits significantly less overall toxicity compared to the traditional Dox drug. It can be explained by the successive release of the incorporated drug during the degradation of the hydrogels in the conditions of the animal organisms. Therefore, the aLap+Dox/hydrogels are the promising carriers of incorporated antitumor drugs.
Investigation of the phenyl dihydrouracil molecules as CRBN ligands for the PROTAC development
Aim. CRBN is the most widely used E3 ligase for PROTACs development due to the large variety of its glutarimide ligands, which have good drug-like properties and low molecular weight. However, because of the racemization and low stability of glutarimides, the process of drug development faces many challenges [1-2]. This work aims to study and analyze the set of more stable phenyl dihydrouracil molecules as promising binders for CRBN. These investigations will be helpful during the development of PROTACs. Conclusions. The IC50 value of tested phenyl dihydrouracil Compound 1 is similar to the well-known Cereblonglutarimide ligand pomalidomide, which indicates that phenyl dihydrouracils might be a good replacement for the Thalidomide derivatives with the potential to be used during CRBN-based PROTACs development.
Multiplexed High Content Imaging assay optimization for the analysis of apoptosis/necrosis in breast cancer cells after treatment with Vorinostat analogues
Aim. Vorinostat is ahistone deacetylase inhibitor approved for the treatment of acute T-cell lymphoma The recent studies have shown a significant potential of Vorinostat in the mono- and polytherapy of breast cancer as well. Administration of Vorinostat causes cell cycle arrest and apoptosis in neoplastic cells both in vivo and in vitro. Several analogues of Vorinostat were synthesized at Enamine Ltd. to improve the pharmacokinetics, selectivity and efficacy of the parental molecule. In this study, we aimed to test the effect of Vorinostat and its analogues on the viability of breast adenocarcinoma MCF-7 cell line using multiplexed High Content Imaging assay. Conclusions. High Content imaging assay coupled with luminescent cytotoxicity assessment was successfully optimized to investigate the potential cytotoxic and apoptotic anticancer effects of Vorinostat analogues in the breast cancer model, laying a foundation for further exploration of their therapeutic potential. We identified optimal conditions for the cell growth and confluency, as well as concentrations for staining solution components and reference compounds.
Development, optimization, and comparison of two versions of ALT-sensitive biosensor based on glutamate oxidase and pyruvate oxidase
Aim. Alanine aminotransferase (ALT) is an enzyme mostly found in heart and liver cells. Therefore, its blood content is often used as a non-selective biomarker of damage to these organs and helps diagnose such diseases as cirrhosis, hepatitis, myocardial infarction, stroke, etc. Since these diseases usually result in a patient’s critical condition requiring immediate medical aid, the availability of a fast, accurate, portable and easy-to-use method for ALT blood level detecting is a necessity. Currently, clinical research of ALT level is conducted using such methods as spectrometry and immunoassay, which can’t meet all the needs of doctors. In contrast, biosensors have the potential for miniaturization, automation, and cost reduction of analysis. Therefore, it was decided to develop biosensors for determining the level of ALT in biological solutions. Conclusions. It was shown that the biosensor based on glutamate oxidase is easier to use and more stable due to the smaller number of coenzymes. However, the biosensor based on pyruvate oxidase is preferred when creating more advanced biosensor system for the simultaneous determination of ALT and AST (another biomarker of heart and liver diseases, which is often determined simultaneously with ALT for more accurate diagnosis and has one common stage of the enzymatic reaction), as it allows to separate the signal from these two enzymes.
Isolation of bacteriophages as therapeutic agents for combating trauma-related infections in Ukraine
Aim. Antimicrobial resistance (AMR) is a huge challenge for all countries. This problem has reached particularly alarming proportions in Ukraine, which has been fighting on the battlefield for its independence for three years now. Priorities to address AMR in human health include research and development of novel antibacterial preparations. In this context due to their unique properties, bacteriophageshave been perceived as promising tools in combating bacterial pathogens. The goals of our work were to investigate the microbiological profiles of wound injuries and to isolate bacteriophages capable of lysing the most relevant causative agents of soft and bone tissue infections. Conclusions. This work has been funded by the National Research Foundation of Ukraine (grant No. 2022.01/0065) and represents the initial large-scale effort to develop a collection of phages targeting relevant bacteria, through the collaboration of multiple institutions. Additional research is required to establish the role of phages in modern medicine, to conduct clinical trials and to facilitate the implementation of phage therapy into clinical practice.
«Smart» hydrogel nanocomposites for biomedical applications
Aim. Application of polymer composites based hydrogels filled by functionalized nanoparticles (acid-modified nanoclay laponite and gold nanoparticles) allows their use for early diagnosis of cancer and filling postoperative cavities, especially after tumor resection. Conclusions. Acid modification of Lap can serve as a basis for the development of the nanocomposite hydrogel diagnostic systems. The synthesized hybrid polymeric materials based on porous polyvinylformal, acrylic hydrogels and gold nanoparticles can be used to fill postoperative cavities with simultaneous targeted release of the incorporated Doxorubicin and Albucide.
Alginate gels and nanocomposites with prolonged release of drugs and plant protection agents
Aim. Over the past few years, researchers have been increasingly focused on natural polymers, which are favorably distinguished from synthetic polymers, primarily by their lack of toxic effects on the humans and environment. This study is devoted to the creation of biosafe vehicles for targeted delivery and controlled release of drugs and plant protection products based on alginate gels and nanocomposites. Conclusions. The methods for synthesis of alginate gels and nanocomposites were developed and their physical and chemical properties were characterized. It was found that the alginate (micro)beads obtained on their basis are suitable for the targeted transport and controlled sustained release of drugs and plant protection agents during a few days.
The effect of plant alkaloid Chelidonin with fullerene C60 carbon nanoparticles on the permeability of hERG potassium channels
Aim. Our study aimed at investigating the effect of plant alkaloid Chelidonin as a monotherapy and in the co-treatment with carbon nanoparticles fullerene C60 on the K+ ion permeability through hERG potassium channel using FluxOR assay. Conclusions. Thus, studies on potassium channels permeability are extremely important due to their wide-ranging effects on various physiological processes. The use of the FluxOR screening assay is an effective tool for identifying molecules that inhibit the cellular hERG potassium channels. The inhibitory effect of Chelidonin on the hERG potassium channels can be reduced by C60 fullerene nanoparticles.
Adaptor protein CIN85 promotes collagen adhesion and invasion of osteosarcoma cells
Aim. This study is aimed at investigation of the CIN85 effect on osteosarcoma (OS) cells collagen adhesion and invasion. Conclusions. Our results demonstrate that increased CIN85 expression in osteosarcoma cells is associated with elevated collagen adhesion and invasion and may thereby contribute to metastasis.
Food additives – carrageenans – in the context of changes in the functional characteristics of body cells
Aim. Currently, varieties of food additives are used in industry, but there are many data in the literature on the safety of carrageenans. There is evidence that degraded carrageenans have a toxic effect on the body. Some authors [1] have proven that λ–carageenan, a mucopolysaccharide extracted from the cell wall of red algae (Chondrus crispus), can induce acute enterocolitis. λ–carrageenans were shown to stimulate the inflammatory process in the body, which contributes to an increase in the blood markers of acute inflammation. In another research [2], semi–refined carrageenan was used as a model for inducing acute enterocolitis in rats. Conclusions. 1. It is possible to use oral administration of 1% carrageenan solution for 14 days as an experimental model of enterocolitis; 2. Under the conditions of λ–carrageenan administration, an acute inflammatory process occurs, which is accompanied by an increase in the content of acute–phase indicators in the blood; 3. There is an increase in the generation of ROS in leukocytes, changes in the phospholipid composition of membranes, which promotes the development of apoptosis; 4. Additional research is needed because the effect of carrageenan on the body is quite complex and inconspicuous.
Antitumor and antimicrobial activity of exometabolites of Black Sea actinobacteria
Aim. The aim is to determine the biotechnological potential of marine actinobacteria in order to assess the prospects for their use as producers of antibiotics and antitumour compounds in the biotechnology of new drugs. Conclusions. The Black Sea strains of actinobacteria Lim9.2 and Lim10 are promising producers of antitumor compounds and antibiotics and can be recommended for use in the biotechnology of new drugs.
Analysis of trends in physiologically based pharmacokinetic modelling in silico in translational studies of monoclonal antibodies
Aim. The aim of the study was to identify trends and directions of using physiologically based pharmacokinetic modelling (PBPK) in silico in translational studies of mABs. Conclusions. Physiologically based pharmacokinetic modelling is used at T0-T3 stages of translational studies of monoclonal antibodies and their fragments, which can be used to solve complex problems in the discovery and development of pharmacotherapeutic agents of this group.
physiologically based pharmacokinetic (PBPK) modelling
Isolation and characterization of extracellular vesicles from different types of mesenchymal stromal/stem cells for future translation research
Aim. The aim of our study was to isolate and characterize EVs from umbilical cord-derived MSCs (UC-MSCs), adipose tissue-derived MSCs (ADSCs) and dental pulp stem cells (DPSCs). Conclusions. UC-MSCs and DPSCs are the most suitable cell types for large-scale EVs isolation. Based on size distribution and CD63/CD81 expression, EVs isolated from UC-MSCs, DPSCs, and ADSCs can be defined as exosomes. UC-MSC-derived EVs contain higher levels of growth factors and cytokines compared to DPSC- and ADSC-derived EVs, which may mediate stronger tissue regeneration through regulation of cell proliferation, immunosuppression, and vasculogenesis.
Prevention of Pseudomonas aeruginosa biofilm formation by pyocins
Aim. To study the ability of pyocins to prevent biofilm formation of P. aeruginosa. Conclusions. A single preventive application of pyocins with 20.5-51.2x103 AU/mL activity affects P. aeruginosa UCM B-3 and UCM B-10 biofilm formation. It prevents the reproduction of microorganisms in planktonic (up to 14500 times) and biofilm (up to 92 times) forms and also slows down the biofilm formation (up to 53%) within 24-48 hours.
prevention of Pseudomonas aeruginosa biofilm formation
Optimization and adaptation of amperometric biosensor based on lactate oxidase for measuring lactate concentration in blood serum samples
Aim. Lactic acid is a crucial human metabolite with numerous physiological roles and applications in various fields. It serves as a biomarker for conditions like hypoxia and kidney and liver issues and is used as a food additive and quality marker for food and beverages. Due to its broad usage, there is a demand for fast, reliable, and easy methods to analyze lactate. Biosensor measurement methods are emerging as they are quick, affordable, easy to use, and portable.This study aims to analyze existing biosensor systems for lactate determination and to adapt and optimize an amperometric biosensor based on lactate oxidase for measuring lactate in blood serum samples. Conclusions. The data obtained using the publication analysis parameters built into bibliographic systems were analyzed, and the directions for the development of biosensor methods of lactate determination were determined. The amperometric biosensor for measuring lactate concentration was optimized and adapted. Analysis of a number of blood serum samples using the proposed biosensor and a standard measurement method was performed and a high correlation of the results was shown.
Engineering designer-recombinases for therapeutic genome editing
Aim. We aim to engineer Y-SSRs to make them suitable for therapeutic genome editing. By reprogramming their DNA-binding specificity to act on human genomic sequences, we aim to excise, integrate, invert or replace DNA sequences to develop curative therapies for genetic diseases. Conclusions. The development of ZFD-dependent recombinases provides a powerful tool for genome editing applications that combines the ease of ZFD targeting with the editing precision of SSRs. Our research markedly expedites the creation of highly effective and precisely targeted designer-recombinases. Specifically, the fusion of a non-specific recombinase guided by ZFD binding to its intended target site introduces a novel concept for the development of precision genome editing tools. This approach expands the repertoire of techniques available for precise genetic modifications, holding promising implications across diverse scientific and biomedical applications. We anticipate that the developed approach could be adapted to other DNA-binding domains and other DNA-modifying enzymes. If successful, this concept would open exciting perspectives for flexible, seamless, and precise genome surgery.
Flow injection biosensor system for real time determination of heavy metal ions for water monitoring
Aim. Heavy metal ion pollution is a worldwide problem that causes irreparable damage to humans and other organisms. The traditional detection methods, while accurate, are expensive, complex, and slow, making them impractical for continuous real-time monitoring. Biosensors, however, offer a promising solution with their affordability, ease of use, sensitivity, portability, and on-site monitoring capabilities, effectively addressing heavy metal ion pollution challenges. Conclusions. A new flow injection biosensor system for real time determination of heavy metal ions for water monitoring was developed. Optimal parameters for continuous flow analysis were determined and its main analytical characteristics were investigated, including sensitivity, detection limit, signal reproducibility, and reactivation after inhibition. The developed biosensor system can potentially be used for the analysis of heavy metals in water.
Reinvigorating antitumor immunity in brain tumors with short peptides and siRNA–nanocarriers targeting the tumor microenvironment
Aim. Tumor cells stimulate molecular, cellular and physical changes within their host tissues creating a tumor microenvironment (TME), a complex and continuously evolving structure which supports tumor growth and progression. Its composition varies between tumor types, but hallmark features include accumulation of myeloid cells, stromal cells, blood vessels, and extracellular matrix. Antitumor immunity is inhibited or eluded by tumor–secreted factors that reprogram infiltrating myeloid cells and create the immunosuppressive TME. Advancements in single–cell techniques allowed us to systemically profile the multiple–omic status of the TME at a single–cell resolution, revealing the phenotypes and functionalities of disease–specific cell populations. Conclusions. The results open up new perspectives in functional genomic studies and therapeutic targeting of microglia in brain tumors and other CNS diseases.
Association between metabolic-associated fatty liver disease and Covid-19 severity: A genetic analysis
Aim. This study aimed to link specific single nucleotide polymorphisms (SNPs) in the IFNAR2 rs2236757, ACE2 rs2074192, OAS1 rs10774671 and OAS3 rs10735079 genes to COVID-19 severity in MAFLD (metabolic-associated fatty liver disease) patients. These genes influence interferon, antiviral responses, and viral entry. Conclusions. This study did not find an association between the genetic parameters investigated and severity of COVID-19 disease in patients with MAFLD. Our findings emphasize the need for further research considering population differences and additional genetic and environmental variables.
Assessing microbial genome representation across various reference databases: A comprehensive evaluation
Aim. Metagenomics research can provide significant insights into the composition, diversity and functions of mixed microbial communities found in various environments. To identify bacterial species, reads from samples are mapped to references that are found in bacterial reference databases. Multiple references may be assigned the same taxonomic identifiers yet these references may contain different genomic information. This project was designed to uncover and correct inconsistencies in bacterial reference databases by comparing species names and genomic representation for the three most commonly used bacterial reference databases (PATRIC, RefSeq and Ensembl). Our first study “Improving the usability and comprehensiveness of microbial databases” [1] considered the concordance of the databases based solely on species names. We extended that research to compare not only the species names but also bacterial genomes and to estimate their similarity. Conclusions. The lack of species and genus overlap not only undermines the accuracy of metagenomic analysis but also emphasizes the critical need for a standardized integration of existing databases. Our analysis will not only enhance the identification and characterization of microbial life but also improve the comparability and rigor of metagenomic research.