Ribonucleic Acid Synthesis Research Articles

Bioinformatics and machine learning-driven key genes screening for vortioxetine

Vortioxetine is a pharmacological agent that acts as a serotonin modulator and stimulant, with safety and tolerability being important health issues. This study aimed to use bioinformatic and machine learning methods to find differentially expressed genes (DEG) between rats exposed to vortioxetine and matched controls. The GSE236207 dataset (Rattus norvegicus) was obtained from the National Center for Biotechnology Information (NCBI) and analyzed with R, followed by genetic ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, and String's protein-protein interaction network was established to identify important genes. The original datasets were preprocessed in the second step by detecting and correcting missing and noisy data and then merged. After feature selection for the cleaned dataset, machine learning algorithms such as the K-nearest neighbors' algorithm, Naive Bayes, and Support Vector Machine (SVM) were used. In addition, an accuracy of 0.90 was observed with SVM. Leveraging these techniques, the study linked IGFBP7, KLRA22, PROB1, SHQ1, NTNG1, and LOC102546359 to vortioxetine exposure. The bioinformatic analysis revealed 18 upregulated genes and 27 downregulated genes, with all approaches identifying only one common locus, LOC102546359, responsible for noncoding ribonucleic acid (ncRNA) synthesis. The crucial point is that this locus bears no connection to any disease or trigger mechanism, thereby bolstering the safety of vortioxetine.

Features of the immunopathogenesis of infections caused by viroids and satellite viruses

One of the main molecular mechanisms of viroids that cause disease in plants is the blocking of ribonucleic acid functions of host cells by viroid ribonucleic acid. The variety of splicing options is due to viroid replication, which requires ribonucleic acid polymerase, ribonuclease, ligase, and deoxyribonucleic acid working on ribonucleic acid matrices. Viroids with faster replication are preferred. Identifying host proteins that interact with viroid ribonucleic acid is critical in the pathogenesis of viroid infections, which leads to gene expression changes of host plants. The study of the pathogenesis of plant infections caused by satellite viruses has shown that they have a common ancestor and that the satellite viruses suppress the reproduction of the helper virus. Satellite viruses require accessory viral proteins to encode capsid proteins for genome encapsulation and reproduction. Replication occurs in the cytoplasm and is induced by ribonucleic acid polymerase of the helper virus. Hepatitis D virus ribonucleic acid replication requires cell ribonucleic acid polymerase II. When the viral and endosomal membranes fuse, the ribonucleic acid of the hepatitis D virus moves into the nucleus, and antigenomic ribonucleic acid is produced, which is the template for the synthesis of matrix ribonucleic acids encoding delta protein. The minor delta antigen regulates ribonucleic acid editing, and the large delta antigen inhibits viral replication and induces a signal for the transport of ribonucleic acid from the cell nucleus to the cytoplasm, which ensures the assembly of new viral particles. Large and small delta antigens have been detected in the brain, liver, lungs, kidneys, and spleen of snakes by reverse transcriptase polymerase chain reaction, Western blotting, and immunohistochemical assays, indicating that all delta viruses possibly share a common ancestor that arose before the divergence of reptiles and mammals.

Costs of ribosomal RNA stabilization affect ribosome composition at maximum growth rate

Ribosomes are key to cellular self-fabrication and limit growth rate. While most enzymes are proteins, ribosomes consist of 1/3 protein and 2/3 ribonucleic acid (RNA) (in E. coli).Here, we develop a mechanistic model of a self-fabricating cell, validated across diverse growth conditions. Through resource balance analysis (RBA), we explore the variation in maximum growth rate with ribosome composition, assuming constant kinetic parameters.Our model highlights the importance of RNA instability. If we neglect it, RNA synthesis is always cheaper than protein synthesis, leading to an RNA-only ribosome at maximum growth rate. Upon accounting for RNA turnover, we find that a mixed ribosome composed of RNA and proteins maximizes growth rate. To account for RNA turnover, we explore two scenarios regarding the activity of RNases. In (a) degradation is proportional to RNA content. In (b) ribosomal proteins cooperatively mitigate RNA instability by protecting it from misfolding and subsequent degradation. In both cases, higher protein content elevates protein synthesis costs and simultaneously lowers RNA turnover expenses, resulting in mixed RNA-protein ribosomes. Only scenario (b) aligns qualitatively with experimental data across varied growth conditions.Our research provides fresh insights into ribosome biogenesis and evolution, paving the way for understanding protein-rich ribosomes in archaea and mitochondria.

Promoting Nucleic Acid Synthesis in Saccharomyces cerevisiae through Enhanced Expression of Rrn7p, Rrn11p, IMPDH, and Pho84p.

Saccharomyces cerevisiae has emerged as a preferred source for industrial production of ribonucleic acids (RNAs) and their derivatives, which find wide applications in the food and pharmaceutical sectors. In this study, we employed a modified RNA polymerase I-mediated green fluorescent protein expression system, previously developed by our team, to screen and identify an industrial S. cerevisiae strain with an impressive 18.2% increase in the RNA content. Transcriptome analysis revealed heightened activity of genes and pathways associated with rRNA transcription, purine metabolism, and phosphate transport in the high nucleic acid content mutant strains. Our findings highlighted the crucial role of the transcription factor Sfp1p in enhancing the expression of two key components of the transcription initiation factor complex, Rrn7p and Rrn11p, thereby promoting rRNA synthesis. Moreover, elevated expression of 5'-inosine monophosphate dehydrogenases, regardless of the specific isoform (IMD2, 3, or 4), resulted in increased rRNA synthesis through heightened GTP levels. Additionally, exogenous phosphate application, coupled with overexpression of the phosphate transporter PHO84, led to a 61.4% boost in the RNA yield, reaching 2050.4 mg/L. This comprehensive study provides valuable insights into the mechanism of RNA synthesis and serves as a reference for augmenting RNA production in the food industry.

ПЕРСПЕКТИВЫ РАЗРАБОТКИ НОВЫХ ОРИГИНАЛЬНЫХ АНТИСЕПТИЧЕСКИХ СРЕДСТВ НА ОСНОВЕ УСНИНОВОЙ КИСЛОТЫ

Introduction. Environment changing not least because of human activities determines the appearance of modified microorganisms. Many pathogens have enhanced their pathogenic properties. Their increasing drug resistance represents quite a serious problem. Among potentially efficient antiseptic substances, usnic acid and its derivatives are greatly emphasized on. Aim of our study was to conduct a narrative review of the prospects for the practical (pharmaceutical) use of usnic acid as an antiseptic. Research Materials. To perform the literature analysis, we used sources from international databases, such as Web of Science, Scopus, and PubMed, as well as from the domestic library system, eLibrary. Results. Usnic acid is found in large amounts in various lichen species. It has quite a broad spectrum of antimicrobial action. Its anti-inflammatory effects and enhancement of tissue regeneration wasproven both experimentally and clinically. The operation of usnic acid and its derivatives is determined by inhibiting the synthesis of ribonucleic acid and breaking the deoxyribonucleic acid replication. Moreover, it has a cytotoxic effect and destroys the membranes of microorganisms. In pharmaceutical industry, usnic acid is produced in many forms, such as powders, capsules, antiseptic gels, creams, and protective tapes. They are used in combined treatment of infectious diseases, in general therapy, in post-burn wound healing procedures, and in dentistry. We have concluded that lichens are very promising as raw materials for isolating usnic acid. It is necessary to search for new highly efficient methods to manufacture and use it in various farmaceutical forms.

Novel molecular mechanism of high ribonucleic acid yield in Saccharomyces pastorianus revealed by transcriptomics

Ribonucleic acid (RNA) and its degradation products find widespread application across various industries, including the food condiments sector. This study employed comparative transcriptomics to investigate the genetic mechanisms underlying RNA synthesis in the mutant Saccharomyces pastorianus strain G03H8, which exhibited a high RNA yield. To identify genetically engineered targets, single gene over-expression and CRISPR/Cas9 gene editing technology were utilized. The differential enrichment results revealed a close association between RNA metabolism and cellular processes such as the cell cycle, purine metabolism, nucleotide metabolism, and other metabolic pathways. Subsequently, we selected the top nine most promising genes to evaluate their impact on RNA synthesis. In these nine targets, upon comparing the RNA yield of the genetically engineered strains, G03-TAL1, G03-PGM2, G03-ΔPRS5, and G03-△DBP8, with the parent strain G03, significant improvements of 31.7%, 41.8%, 72.1%, and 46.7% were observed, respectively. Furthermore, these four genes were found to enhance the strain's growth and augment the pentose phosphate pathway, thus demonstrating the considerable potential for enhancing RNA yield. Notably, this study represents the first instance of identifying the upregulation of TAL1, PGM2, PRS5, and DBP8 as a means to increase RNA content in S. pastorianus. Consequently, our findings present novel genetic targets for enhancing RNA production and contribute to a deeper understanding of the mechanisms involved in high RNA synthesis in S. pastorianus.

Polyamine, 1,3-diaminopropane, regulates defence responses on growth, gas exchange, PSII photochemistry and antioxidant system in wheat under arsenic toxicity

The metalloid arsenic (As) is extremely hazardous to all living organisms, including plants. Pollution with As is very detrimental to the photosynthetic machinery, cell division, energy generation, and redox status. In order to cope with stress, the use of growth regulators such as polyamines (PA), which strengthen the antioxidant system of plants, has become widespread in recent years. PAs can modulate the plant growth through basic mechanisms common to all living organisms, such as membrane stabilization, free radical scavenging, deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and protein synthesis, enzyme activities and second messengers. However, the effect of 1,3- diaminopropane (Dap), which is a product of PA catabolism, is not clear enough in plants exposed to As toxicity. In the current study, the different concentrations of 1,3-diaminopropane (0.1, 0.5 and 1 mM Dap) were hydroponically treated to wheat (Triticum aestivum) under arsenic stress (100 μM As) and then relative growth rate (RGR), relative water content (RWC), proline content (Pro), gas exchange parameters, PSII photochemistry, chlorophyll fluorescence kinetics, antioxidant activity and lipid peroxidation were assessed. RGR, RWC, osmotic potential and Pro content decreased in As-applied plants. The inhibition of these parameters could be reversed by Dap treatments. Besides, Dap applications mitigated the As toxicity-induced suppression on chlorophyll fluorescence (Fv/Fm, Fv/Fo and Fo/Fm) and the performance of PSII photochemistry. As impaired the balance on antioxidant capacity by decreased activities of catalase (CAT), peroxidase (POX), glutathione peroxidase (GPX), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and the contents of ascorbate (AsA) and glutathione (GSH) and then lipid peroxidation (TBARS content) increased. In the presence of Dap under As stress, the plants exhibited an increase in superoxide dismutase (SOD), POX, and GPX. Dap treatments contributed to the maintenance of cellular redox state (AsA/DHA and GSH/GSSG) by regulating the activities/contents of enzyme/non-enzyme involved in the AsA-GSH cycle. After Dap applications against stress, ROS accumulation (H2O2 content) and lipid peroxidation (TBARS) were effectively reduced. The findings showed that by eliminating As-induced oxidative damage and protecting the biochemical processes of photosynthesis, Dap treatments have a substantial potential to give resistance to wheat.

Ribonucleic Acid Nucleotides in Maternal and Fetal Tissues Derive almost Exclusively From Synthesis de novo in Pregnant Mice

The contributions of dietary nucleotides and nucleotides synthesized de novo to ribonucleic acid synthesis in vivo were estimated by feeding, from d 13 to 18 of gestation, two groups of five pregnant mice a defined diet that contained either uniformly [U13C]-labeled nucleotides or [U13C]-algal amino acids isolated from algal biomass. Ribonucleic acid and protein were isolated from mucosa, liver and fetus. Nucleosides and amino acids were isolated and converted to their trimethylsilyl and n-propyl ester, heptaflurobutyramide derivatives, respectively. The isotopic enrichments of all isotopomers were determined by gas chromatography-mass spectrometry. In the mice that ingested [U13C]-nucleotides, the isotopic enrichment of [U13C]-purines (0.03–0.2 mol/100 mol) was significantly (P < 0.001) less than that of [U13C]-uridine (1.5–4.2 mol/100 mol). [13C5]-Purines (0.1–0.8 mol/100 mol) and [13C4]-uridine (0.2–0.5 mol/100 mol) were detected, showing that some dietary bases and ribose were incorporated via the salvage pathway. In mice that ingested U13C-amino acids, the isotopic enrichment (2–4.6 mol/100 mol) of the [13C2]-purines, which derive from [U13C]-glycine, was between 73 (liver) and 113% (fetus) of protein-bound 13C2-glycine. The isotopic enrichment (0.8–1.6 mol/100 mol) of [13C3]-uridine, an isotopomer that derives from [U13C]-aspartate, was 50 (liver) to 126% (mucosa) of [13C4]-protein-bound aspartate. The results suggest that a large majority of the bases incorporated into maternal and fetal ribonucleic acids derive from synthesis de novo.

CPEB3 low-complexity motif regulates local protein synthesis via protein–protein interactions in neuronal ribonucleoprotein granules

Biomolecular condensates, membraneless organelles found throughout the cell, play critical roles in many aspects of cellular function. Ribonucleoprotein granules (RNPs) are a type of biomolecular condensate necessary for local protein synthesis and are involved in synaptic plasticity and long-term memory. Most of the proteins in RNPs possess low-complexity motifs (LCM), allowing for increased promiscuity of protein-protein interactions. Here, we describe the importance of protein-protein interactions mediated by the LCM of RNA-binding protein cytoplasmic polyadenylation element binding protein 3 (CPEB3). CPEB3 is necessary for long-term synaptic plasticity and memory persistence, but the mechanisms involved are still not completely elucidated. We now present key mechanisms involved in its regulation of synaptic plasticity. We find that CPEB3-LCM plays a role in appropriate local protein synthesis of messenger ribonucleic acid (mRNA) targets, through crucial protein-protein interactions that drive localization to neuronal Decapping protein 1 (DCP1)-bodies. Translation-promoting CPEB3 and translation-inhibiting CPEB1 are packaged into neuronal RNP granules immediately after chemical long-term potentiation is induced, but only translation-promoting CPEB3 is repackaged to these organelles at later time points. This localization to neuronal RNP granules is critical for functional influence on translation as well as overall local protein synthesis (measured as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) insertion into the membrane and localization to the synapse). We therefore conclude that protein-protein interaction between the LCM of CPEB3 plays a critical role in local protein synthesis by utilizing neuronal RNP granules.

Thermal resistance of Escherichia coli O157:H7 in laboratory media, milk, and beef extracts during non-isothermal processing at various heating rates

This study investigated the effect of non-isothermal treatments with different heating rates (HRs) on inactivating Escherichia coli O157:H7 in various heating media. E. coli O157:H7 in phosphate-buffered saline (pH 7; PBS), Luria-Bertani broth with (LBS) or without (LB) 1% NaCl, milk, 3% beef extract (beef3%), and 30% beef extract (beef30%) were inactivated under non-isothermal conditions (up to 50 - 60 °C) using various HRs between 1.32 and 10.78 °C/min. After treatment with an HR of 1.32 °C/min to a target temperature of 60 °C, the reduction level of E. coli O157:H7 were 6.49, 2.28, 1.20, 1.30, 5.55 and 5.02 log CFU/mL in PBS, LB, LBS, milk, beef3%, and beef30%, respectively. Contrastingly, E. coli O157:H7 treated in PBS, LB, milk, beef3%, and beef30% with an HR of 10.78 °C/min to the same target temperature were completely inactivated to not-detectable level. Moreover, E. coli O157:H7 treated at 10.63 °C/min exhibited more severe morphological injuries than those at 2.23 °C/min. Interestingly, inactivation through non-isothermal treatment is potentially involved in either ribonucleic acid or lipid synthesis, as E. coli O157:H7 treated at 10.63 °C/min for 3.5 min less recovered on TSA with rifampicin and streptomycin. These observations highlight the ability of the E. coli O157:H7 to survive for long periods at a potentially sub-lethal temperature, which may be enhanced concomitantly with a decrease in the HR of the non-isothermal treatment.

Medicatiefouten met methotrexaat: casuïstiek en opportuniteiten door de bril van de ziekenhuisapotheker

Medication errors with methotrexate: new insights into an old drug Methotrexate (MTX) was first used in 1948 to treat childhood leukaemia. Nowadays, it is used for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis and inflammatory bowel disease. MTX is a folic acid antagonist that binds dihydrofolate reductase and thereby inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins. As an incontestable cornerstone in the treatment of RA, MTX should be started as soon as RA is diagnosed. The primary goal of the treatment is rapid and effective disease control to prevent long-term damage to the joints. For the treatment of patients with RA, the usual starting dose of MTX is 7.5-10 mg per week. Based on the clinical response, the dose could be increased to reach the optimal dose. The most common adverse drug events of MTX therapy are gastro-intestinal intolerance, haematological abnormalities, alopecia, hepatotoxicity and pulmonary toxicity. Overall, MTX is well tolerated. However, fatal cases of MTX intoxication have been reported in literature, mainly due to the daily intake and thus overdose of MTX. Despite the widespread experience with MTX, medication errors still occur with a risk of potentially severe adverse drug events. Clinical pharmacy interventions aim to detect these medication errors in inpatients. Based on a case series within a hospital population, the most common medication errors with MTX are presented. Subsequently, specific interventions to optimize medication safety with MTX therapy are described. The implementation of a specific chemotherapy module in the computerized physician order entry and clinical pharmacy interventions, such as medication reconciliation, the engagement of clinical pharmacists on hospital wards as part of the interdisciplinary team and prescription validation based on clinical rules, can contribute to a safer use of MTX.

MicroRNA-21 guide and passenger strand regulation of adenylosuccinate lyase-mediated purine metabolism promotes transition to an EGFR-TKI-tolerant persister state

In EGFR-mutant lung cancer, drug-tolerant persister cells (DTPCs) show prolonged survival when receiving EGFR tyrosine kinase inhibitor (TKI) treatments. They are a likely source of drug resistance, but little is known about how these cells tolerate drugs. Ribonucleic acids (RNAs) molecules control cell growth and stress responses. Nucleic acid metabolism provides metabolites, such as purines, supporting RNA synthesis and downstream functions. Recently, noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), have received attention due to their capacity to repress gene expression via inhibitory binding to downstream messenger RNAs (mRNAs). Here, our study links miRNA expression to purine metabolism and drug tolerance. MiR-21-5p (guide strand) is a commonly upregulated miRNA in disease states, including cancer and drug resistance. However, the expression and function of miR-21-3p (passenger strand) are not well understood. We found that upregulation of miR-21-5p and miR-21-3p tune purine metabolism leading to increased drug tolerance. Metabolomics data demonstrated that purine metabolism was the top pathway in the DTPCs compared with the parental cells. The changes in purine metabolites in the DTPCs were partially rescued by targeting miR-21. Analysis of protein levels in the DTPCs showed that reduced expression of adenylosuccinate lyase (ADSL) was reversed after the miR-21 knockdown. ADSL is an essential enzyme in the de novo purine biosynthesis pathway by converting succino-5-aminoimidazole-4-carboxamide riboside (succino-AICAR or SAICAR) to AICAR (or acadesine) as well as adenylosuccinate to adenosine monophosphate (AMP). In the DTPCs, miR-21-5p and miR-21-3p repress ADSL expression. The levels of top decreased metabolite in the DTPCs, AICAR was reversed when miR-21 was blocked. AICAR induced oxidative stress, evidenced by increased reactive oxygen species (ROS) and reduced expression of nuclear factor erythroid-2-related factor 2 (NRF2). Concurrently, miR-21 knockdown induced ROS generation. Therapeutically, a combination of AICAR and osimertinib increased ROS levels and decreased osimertinib-induced NRF2 expression. In a MIR21 knockout mouse model, MIR21 loss-of-function led to increased purine metabolites but reduced ROS scavenging capacity in lung tissues in physiological conditions. Our data has established a link between ncRNAs, purine metabolism, and the redox imbalance pathway. This discovery will increase knowledge of the complexity of the regulatory RNA network and potentially enable novel therapeutic options for drug-resistant patients.

Delivering an mRNA vaccine using a lymphatic drug delivery device improves humoral and cellular immunity against SARS-CoV-2.

The exploration and identification of safe and effective vaccines for the SARS-CoV-2 pandemic have captured the world's attention and remains an ongoing issue due to concerns of balancing protection against emerging variants of concern while also generating long-lasting immunity. Here, we report the synthesis of a novel messenger ribonucleic acid encoding the spike protein in a lipid nanoparticle formulation (STI-7264) that generates robust humoral and cellular immunity following immunization of C57Bl6 mice. In an effort to improve immunity, a clinically focused lymphatic drug delivery device (MuVaxx) was engineered to modulate immune cells at the injection site (epidermis and dermis) and draining lymph node (LN) and tested to measure adaptive immunity. Using MuVaxx, immune responses were elicited and maintained at a 10-fold dose reduction compared to traditional intramuscular (IM) administration as measured by anti-spike antibodies, cytokine-producing CD8 T cells, neutralizing antibodies against the Washington (wild type) strain and South African (Beta) variants, and LN-resident spike-specific memory B cells. Remarkably, a 4-fold-elevated T cell response was observed in MuVaxx-administered vaccination compared to that of IM-administered vaccination. Thus, these data support further investigation into STI-7264 and lymphatic-mediated delivery using MuVaxx for SARS-CoV-2 and VoC vaccines.

PECULIARITIES OF OXIDATIVE STRESS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITH IRON DEFICIENCY ANEMIA

The article presents changes in hemogram and oxidative stress in patients with acute myocardial infarction (AMI) on the background of iron deficiency anemia (IDA). Iron deficiency anemia is an additional factor that contributes to the deepening of myocardial ischemia and deepens the processes of peroxidation and damage to cardiomyocytes, which is an important factor in the unfavorable course, both acute period and recovery processes in myocardial necrosis. In order to study the indicators of the general analysis of blood and functional state of the antioxidant system in patients with acute myocardial infarction with IDA, 36 patients with AMI with IDA were examined, including 39% men and 61% women. The first group consisted of 10 patients with AMI without IDA, the second 26 patients with AMI and IDA of varying severity, the control group consisted of 30 healthy individuals. Hemogram parameters, glutathione system function, oxyproline, arginase and magnesium levels in the blood were determined. It has been established that women with mild and moderate anemia predominate among patients with acute myocardial infarction with concomitant iron deficiency anemia. Among men, half of the patients have severe anemia. In addition to a decrease in Hb levels, patients with ACS with IDA have the following laboratory signs of anemia: a tendency to increase the average concentration of hemoglobin in one erythrocyte, low serum iron levels and an increase in serum transferrin levels. In the presence of IDA in patients with ACS there are changes in the antioxidant system. Anemic syndrome in such patients is accompanied by increased concentrations of glutathione transferase and peroxidase, as well as decreased concentrations of oxyproline.&#x0D; Anemia can trigger oxidative stress, and an increase in OS may be associated with changes in cardiac function. Possible cardiovascular effects in patients with comorbid conditions should also be considered.&#x0D; Iron deficiency is the most prevalent micronutrient disorder globally. When severe, iron deficiency leads to anemia, which can be deleterious to cardiac function. Given the central role of iron and oxygen in cardiac biology, multiple pathways are expected to be altered in iron-deficiency anemia, and identifying these requires an unbiased approach.&#x0D; Oxidative stress is an imbalance between free radicals and antioxidant molecules that can play an important role in the pathogenesis of iron-deficiency anemia (IDA).&#x0D; Maintenance of the iron homeostasis is essential for metabolic and physiological processes. Iron plays a critical role in erythropoiesis, is incorporated into erythroblasts and reticulocytes, and has a crucial role in oxygen transport and oxygen storage. Moreover, iron is essential for cardiac and skeletal muscle metabolism, the synthesis and degradation of proteins, lipids, ribonucleic acids, and mitochondrial function.&#x0D; Research has now focused on non-traditional cardiovascular risk factors and the roles of iron and iron deficiency (ID) in patients with cardiovascular disease.&#x0D; The Iron required for immune response, hormonal balance, and plays an important role in regulating oxidative stress and aerobic metabolism. The myocardial tissue has a mainly aerobic cellular metabolism, which depends of mitochondria's Krebs cycle enzymes that need iron as an essential cofactor. In this regard, there is some evidence that myocardial iron deficiency is highly prevalent in HF and may play a role in the progression of the disease.

Evaluating serum level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil.

BackgroundKeloids are fibrous lesions formed at the site of trauma due to types I and III collagen irregular production. The presence of thymidylate synthase (TS) is a must for DNA synthesis and repairs causing cell death. 5-fluorouracil (5-FU) is a fluorinated pyrimidine analogue acting as an anti-metabolic agent that inhibits thymidylate synthase and interferes with ribo-nucleic acid (RNA) synthesis.Objectiveswe aimed to evaluate the level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil.MethodsThe study included 20 keloid patients and 20 healthy subjects as a control. Serum TS was estimated using commercially available enzyme-linked immunosorbent assay (ELISA) kits before and after treatment with 5-fluorouracil.ResultsThere was a statistically significant difference in TS levels before and after 5-FU treatment (p < 0.05). Also, results have shown that 5-FU injection has good satisfactory results in treatment of keloid causing reduction in scar volume and symptoms improvement (90% of the patients improved). On the other hand, there was no statistically significant difference in TS levels and the outcomes of the treatment.ConclusionOur findings suggest that intralesional 5-FU injection in keloid has very satisfactory results. However, thymidylate synthase enzyme has a minimal role in evaluating the treatment of keloid, so further studies are required to elaborate the relation between this enzyme and keloid scars.

N6 -methyladenosine Steers RNA Metabolism and Regulation in Cancer.

As one of the most studied ribonucleic acid (RNA) modifications in eukaryotes, N6‐methyladenosine (m6A) has been shown to play a predominant role in controlling gene expression and influence physiological and pathological processes such as oncogenesis and tumor progression. Writer and eraser proteins, acting opposite to deposit and remove m6A epigenetic marks, respectively, shape the cellular m6A landscape, while reader proteins preferentially recognize m6A modifications and mediate fate decision of the methylated RNAs, including RNA synthesis, splicing, exportation, translation, and stability. Therefore, RNA metabolism in cells is greatly influenced by these three classes of m6A regulators. Aberrant expression of m6A regulators has been widely reported in various types of cancer, leading to cancer initiation, progression, and drug resistance. The close links between m6A and cancer shed light on the potential use of m6A methylation and its regulators as prognostic biomarkers and drug targets for cancer therapy. Given the notable effects of m6A in reversing chemoresistance and enhancing immune therapy, it is a promising target for combined therapy. Herein, we summarize the recent discoveries on m6A and its regulators, emphasizing their influences on RNA metabolism, their dysregulation and impacts in diverse malignancies, and discuss the clinical implications of m6A modification in cancer.

Effectiveness of 5-Fluorouracil 5% Cream in Perianal Condylomata Accuminata Treatment: A Case Report

Background: Condylomata accuminata is a sexually transmitted disease, appeared as verrucous or cauliflower-like papules or warts in the anogenital. It is caused by human papillomavirus (HPV), mostly type 6 and 11. The ideal therapy should be simple, inexpensive, effective, does not cause side effects, and can be used by the patient himself. Purpose: To assess the effectiveness of 5-Fluorouracil (5-FU) 5% cream therapy for perianal condylomata accuminata treatment. Case: A 24-year-old male presented with a chief complaint of warts around the anal area that multiplied in the past 3 weeks. The acetowhite test was positive. The patient was diagnosed with condylomata accuminata perianal. The patient received 5-FU 5% cream, applied 3 times a week to the lesions for 5 weeks. After 5 weeks, no new warts were found. Discussion: 5-FU 5% cream is a therapeutic option for perianal wart lesions that easily applied, inexpensive, effective, does not cause side effects, and can be used by the patient himself. It is well known as an antimetabolite with a cytotoxic effect that occurs through a mechanism of disruption in the normal synthesis and function of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). The treatment with 5-FU 5% cream 3 times a week for 5 weeks provided good results with no side effects were reported. Conclusion: The application of 5-FU 5% cream was a modality of self-application treatment that effective for perianal condylomata accuminata.

Analysis of the molecular basis of Saccharomyces cerevisiae mutant with high nucleic acid content by comparative transcriptomics

Ribonucleic acid (RNA) and its degradation products are important functional components widely used in the food industry. Transcription analysis was used to explore the genetic mechanism underlying nucleic acid synthesis in the chemical mutant Saccharomyces cerevisiae strain BY23-195 with high nucleic acid content. Results showed that ribosome biogenesis, meiosis, RNA transport, mitogen-activated protein kinase (MAPK) signaling pathway, tryptophan metabolism, carbon metabolism, and longevity regulating pathway are closely related to the high nucleic acid metabolism of S. cerevisiae. Fourteen most promising genes were selected to evaluate the effect of single-gene deletion or overexpression on the RNA synthesis of S. cerevisiae. Compared with the RNA content of the parent strain BY23, that of mutant strains BY23-HXT1, BY23-ΔGSP2 and BY23-ΔCTT1 increased by 8.19%, 11.60% and 14.00%, respectively. The possible reason why HXT1, GSP2, and CTT1 affect RNA content is by regulating cell fitness. This work was the first to report that regulating the transcription of HXT1, GSP2, and CTT1 could increase the RNA content of S. cerevisiae. This work also provides valuable knowledge on the genetic mechanism of high nucleic acid synthesis in S. cerevisiae and new strategies for increasing its RNA content.

Role of structural and functional proteins of SARS -COV-2

Severe acute respiratory corona virus-2 (SARS-CoV-2) is a ribonucleic acid (RNA) virus with enveloped no-segmented positive sense belonging to a beta (β) - corona virus family. It has 29,903 nucleotides sized genome with 10 open reading frames (ORF). ORF1 (ab) encodes two polypeptides pp1a and pp1b cleaved into 16 functional proteins, which are mainly intended to form replication transcription complex (RTC). The cleavage process of pp1a and pp1b polypeptides to 16 functional proteins of SARs-CoV-2 is mainly facilitated by main protease and papain-like protease. The replication transcription complex (RTC) formed by the action of 16-functional proteins of SARs-CoV-2 is mainly involved as viral RNA synthesis machinery in the transcriptional and replication process of viral RNAs. ORF (2-10) encodes for structural (for example: spike (S), membrane (M), nucleocapsid (N), and envelop (E)) and accessory proteins of SARs-CoV-2. The main functions of structural proteins are viral assembly, viral coating, viral entry into host cells and assembly of the RNA genome. Accessory proteins are proteins that are not involved in the viral synthesis machinery, as 16 functional proteins, and in the viral assembly, coating, entry into host cells and packaging of Viral RNAs, as structural proteins. Rather, these are proteins that may play central role by enhancing viral assembly process, virulence and pathogenesis of SARs-CoV-2. Our aim in the current review was to elaborate the specific role of these structural and functional proteins on viral genomic replication and transcription, viral assembly, host cell attachment and pathogenesis. Multiple literatures have been reviewed to achieve the objective of this review.

Evryscope and K2 Constraints on TRAPPIST-1 Superflare Occurrence and Planetary Habitability

Abstract The nearby ultracool dwarf TRAPPIST-1 possesses several Earth-sized terrestrial planets, three of which have equilibrium temperatures that may support liquid surface water, making it a compelling target for exoplanet characterization. TRAPPIST-1 is an active star with frequent flaring, with implications for the habitability of its planets. Superflares (stellar flares whose energy exceeds 1033 erg) can completely destroy the atmospheres of a cool star’s planets, allowing ultraviolet radiation and high-energy particles to bombard their surfaces. However, ultracool dwarfs emit little ultraviolet flux when quiescent, raising the possibility of frequent flares being necessary for prebiotic chemistry that requires ultraviolet light. We combine Evryscope and Kepler observations to characterize the high-energy flare rate of TRAPPIST-1. The Evryscope is an array of 22 small telescopes imaging the entire Southern sky in g′ every two minutes. Evryscope observations, spanning 170 nights over 2 yr, complement the 80 day continuous short-cadence K2 observations by sampling TRAPPIST-1's long-term flare activity. We update TRAPPIST-1's superflare rate, finding a cumulative rate of superflares per year. We calculate the flare rate necessary to deplete ozone in the habitable-zone planets’ atmospheres, and find that TRAPPIST-1's flare rate is insufficient to deplete ozone if present on its planets. In addition, we calculate the flare rate needed to provide enough ultraviolet flux to power prebiotic chemistry. We find TRAPPIST-1's flare rate is likely insufficient to catalyze some of the Earthlike chemical pathways thought to lead to ribonucleic acid synthesis, and flux due to flares in the biologically relevant UV-B band is orders of magnitude less for any TRAPPIST-1 planet than has been experienced by Earth at any time in its history.