Deoxyribonucleic Acid Replication Research Articles

Distinctive expression of DNA replication factors in squamous cell carcinomas of the lip, face and oral cavity

ObjectiveUncontrolled proliferation and aberrations in cell-cycle progression are fundamental issues in cancer. In this study we aimed to determine and compare deoxyribonucleic acid (DNA) replication licensing factors at the mRNA and protein levels among squamous cell carcinomas (SCCs) of the lip, facial-skin and oral cavity. Materials and methodsA total of 103 lip, oral and face SCCs were immunohistochemically stained with MCM2 (mini-chromosome maintenance 2), geminin, and ki67, and their labeling-indices were calculated. Also, 57 SCCs from the same regions along with their adjacent normal tissues underwent quantitative reverse transcription-polymerase chain reaction analysis. ResultsAll three proteins were overexpressed in the studied SCCs, but only geminin (P = 0.004) showed significant difference among the three regions, with higher levels in oral SCCs compared to lip (P = 0.005) and skin (P = 0.024) tumors. Geminin expression did not differ between skin- and lip-SCCs (P = 0.822). MCM2/ki67 ratio was higher in oral- compared to skin-neoplasms (P = 0.039), but no difference was found in geminin/ki67 among the SCC-subsites. There were significant differences in MCM2 and geminin mRNA between carcinomatous- and normal-tissues in all tumors, but not among the three locations. ConclusionMCM2 and geminin are involved in the tumorigenesis of lip, face and oral SCC at both mRNA- and protein-levels. Geminin may have a role in the site-specific biologic behavior of SCC. Skin SCCs had the highest proportion of licensed non-proliferating cells, while actively proliferating cells were more prominent in oral tumors. Regarding DNA replication, lip SCCs seem to be closer to skin tumors compared to their oral counterparts.

Structural Insights Into Tautomeric Dynamics in Nucleic Acids and in Antiviral Nucleoside Analogs.

DNA (2′-deoxyribonucleic acid) and RNA (ribonucleic acid) play diverse functional roles in biology and disease. Despite being comprised primarily of only four cognate nucleobases, nucleic acids can adopt complex three-dimensional structures, and RNA in particular, can catalyze biochemical reactions to regulate a wide variety of biological processes. Such chemical versatility is due in part to the phenomenon of nucleobase tautomerism, whereby the bases can adopt multiple, yet distinct isomeric forms, known as tautomers. For nucleobases, tautomers refer to structural isomers that differ from one another by the position of protons. By altering the position of protons on nucleobases, many of which play critical roles for hydrogen bonding and base pairing interactions, tautomerism has profound effects on the biochemical processes involving nucleic acids. For example, the transient formation of minor tautomers during replication could generate spontaneous mutations. These mutations could arise from the stabilization of mismatches, in the active site of polymerases, in conformations involving minor tautomers that are indistinguishable from canonical base pairs. In this review, we discuss the evidence for tautomerism in DNA, and its consequences to the fidelity of DNA replication. Also reviewed are RNA systems, such as the riboswitches and self-cleaving ribozymes, in which tautomerism plays a functional role in ligand recognition and catalysis, respectively. We also discuss tautomeric nucleoside analogs that are efficacious as antiviral drug candidates such as molnupiravir for coronaviruses and KP1212 for HIV. The antiviral efficacy of these analogs is due, in part, to their ability to exist in multiple tautomeric forms and induce mutations in the replicating viral genomes. From a technical standpoint, minor tautomers of nucleobases are challenging to identify directly because they are rare and interconvert on a fast, millisecond to nanosecond, time scale. Nevertheless, many approaches including biochemical, structural, computational and spectroscopic methods have been developed to study tautomeric dynamics in RNA and DNA systems, and in antiviral nucleoside analogs. An overview of these methods and their applications is included here.

Transcriptome Analysis Revealed the Symbiosis Niche of 3D Scaffolds to Accelerate Bone Defect Healing.

Three dimension (3D) printed scaffolds have been shown to be superior in promoting tissue repair, but the cell‐level specific regulatory network activated by 3D printing scaffolds with different material components to form a symbiosis niche have not been systematically revealed. Here, three typical 3D printed scaffolds, including natural polymer hydrogel (gelatin‐methacryloyl, GelMA), synthetic polymer material (polycaprolactone, PCL), and bioceramic (β‐tricalcium phosphate, β‐TCP), are fabricated to explore the regulating effect of the symbiotic microenvironment during bone healing. Enrichment analysis show that hydrogel promotes tissue regeneration and reconstruction by improving blood vessel generation by enhancing oxygen transport and red blood cell development. The PCL scaffold regulates cell proliferation and differentiation by promoting cellular senescence, cell cycle and deoxyribonucleic acid (DNA) replication pathways, accelerating the process of endochondral ossification, and the formation of callus. The β‐TCP scaffold can specifically enhance the expression of osteoclast differentiation and extracellular space pathway genes to promote the differentiation of osteoclasts and promote the process of bone remodeling. In these processes, specific biomaterial properties can be used to guide cell behavior and regulate molecular network in the symbiotic microenvironment to reduce the barriers of regeneration and repair.

Real-time prediction of science student learning outcomes using machine learning classification of hemodynamics during virtual reality and online learning sessions

Current data sources used for the prediction of student outcomes average about 55% accuracy and require a significant amount of input data and time for researchers and educators to produce predictive models of student outcomes. The aim of this study is to examine how neurocognitive data collected via functional near infrared spectroscopy (fNIRS) may be used to create predictive models of student outcomes with greater speed and accuracy when using a synthetic adaptive learning environment (SALEs). Specifically, this study examines the utility of using neurocognitive data to develop student response prediction on a science content test. Participants were recruited from schools located in the United States ( n = 40). Participants in the study engaged in three conditions: no content, video and virtual reality. The lesson video and virtual reality lesson provides an explanation of deoxyribonucleic acid replication. Observed neurocognitive responses were collected during each condition and used to predict the success of student responses on an assessment. On average the predicative accuracy of this approach is 85% and occur within 300 ms. Predictive error rates are less than 15%. Results of this study provides evidence to support the use of neurocognitive data for adaption of digitally presented content and how machine learning approaches and artificial intelligence may be used to classify student data in real-time as students engage with content. Results also illustrate good accuracy and capture of moment-to- moment fluctuations of cognition in real-time. These findings may help the development of artificially intelligent tutors and improve student-based learning analytics. • Classification of neurocognitive data lends itself to prediction of student outcomes. • Describes neurocognitive data sources for development of predictive learning platforms. • Hemodynamic response can help to understand levels of student attention and engagement.

Big Data Information under Proportional Hazard Mathematical Model in Analysis of Hepatitis B Virus Infection Data of Patients with Interventional Liver Cancer through Antiviral Therapy of Entecavir.

The objective of this study was to analyze the application of proportional hazard mathematical model (PHMM) in Hepatitis B Virus (HBV) infection analysis of interventional liver cancer patients treated with entecavir, so as to provide data support for clinical diagnosis and treatment. Based on the survival analysis, the treatment factor x was undertaken as an independent variable to perform linear regression. The regression model took the hazard rate function as the dependent variable to establish an exponential regression equation to construct a PHMM. 136 patients with primary liver cancer receiving interventional chemoembolization combined with the drug (entecavir) were selected as the experimental group, who were in the computer gene expression omnibus (GEO). 87 patients with primary liver cancer who underwent interventional chemoembolization therapy without antiviral treatment were taken as the control group. The PHMM was adopted for comprehensive analysis. In addition, the factors affecting the virological response to antiviral therapy were analyzed using the multiple logistic regression. The results revealed that HBV deoxyribonucleic acid (DNA) negative conversion rate, Hepatitis B e-Antigen (HBeAg) negative conversion rate, and HBeAg serological conversion rate in the experimental group were much higher than those in the control group (P < 0.05). HBV DNA level and proportion of HBsAg <100 IU/mL in the experimental group were much lower than those in the control group (P < 0.05). The virological breakthrough rate and incidence of adverse events at week 24 in the experimental group were greatly lower than those in the control group (P < 0.05). The adverse virological response of patient was positively correlated with HBV DNA load and HBeAg status and negatively correlated with alanine aminotransferase (ALT) level (P < 0.05). Therefore, entecavir can significantly inhibit HBV DNA replication in patients with liver cancer, showing high antiviral effect. High baseline HBV DNA load, positive HBeAg, and low baseline alanine aminotransferase levels were independent risk factors for adverse virology response to entecavir antiviral therapy, which provided a reference for the selection of antiviral drugs for HBV infection.

Discovery and characterization of potent And-1 inhibitors for cancer treatment.

Acidic nucleoplasmic DNA‐binding protein 1 (And‐1), an important factor for deoxyribonucleic acid (DNA) replication and repair, is overexpressed in many types of cancer but not in normal tissues. Although multiple independent studies have elucidated And‐1 as a promising target gene for cancer therapy, an And‐1 inhibitor has yet to be identified. Using an And‐1 luciferase reporter assay to screen the Library of Pharmacologically Active Compounds (LOPAC) in a high throughput screening (HTS) platform, and then further screen the compound analog collection, we identified two potent And‐1 inhibitors, bazedoxifene acetate (BZA) and an uncharacterized compound [(E)‐5‐(3,4‐dichlorostyryl)benzo[c][1,2]oxaborol‐1(3H)‐ol] (CH3), which specifically inhibit And‐1 by promoting its degradation. Specifically, through direct interaction with And‐1 WD40 domain, CH3 interrupts the polymerization of And‐1. Depolymerization of And‐1 promotes its interaction with E3 ligase Cullin 4B (CUL4B), resulting in its ubiquitination and subsequent degradation. Furthermore, CH3 suppresses the growth of a broad range of cancers. Moreover, And‐1 inhibitors re‐sensitize platinum‐resistant ovarian cancer cells to platinum drugs in vitro and in vivo. Since BZA is an FDA approved drug, we expect a clinical trial of BZA‐mediated cancer therapy in the near future. Taken together, our findings suggest that targeting And‐1 by its inhibitors is a potential broad‐spectrum anti‐cancer chemotherapy regimen.

High expression of Ran binding protein 1 predicts poor outcomes in hepatocellular carcinoma patients: a Cancer Genome Atlas database analysis.

Ran-specific binding protein 1 (RANBP1) is involved in the regulation of the cell cycle, while its role in hepatocellular carcinoma (HCC) is unknown. Therefore, we aimed to demonstrate the association of RANBP1 with clinicopathologic features and potential biological functions in HCC based on The Cancer Genome Atlas (TCGA) data. We assessed RANBP1 expression and its correlation with clinicopathologic features and evaluated the prognostic value of RANBP1 with Kaplan-Meier survival analysis and the MethSurv database. Univariate and multivariate Cox regression analyses were conducted to elucidate the factors responsible for prognosis. The identification of a co-expression network and the analysis of related biological events with RANBP1 in HCC were assessed using LinkedOmics. Moreover, gene set enrichment analysis (GSEA) was employed to annotate the biological function of RANBP1. We also explored the correlation between RANBP1 and tumor immune infiltrates using a single sample GSEA (ssGSEA). The expression of RANBP1 was found significantly elevated in HCC and linked to advanced T stage and histopathological grade. Up-regulated RANBP1 expression was linked to poor prognosis. High DNA methylation levels of RANBP1 were significantly linked to very poor overall survival (OS). Co-expression network analysis revealed that RANBP1 was involved in ribosome, spliceosome, deoxyribonucleic acid (DNA) replication, ribonucleic acid (RNA) transport, and cell cycle. GSEA showed enrichment of G2M-checkpoint, Wingless and Int-1 (Wnt) cell signaling, and DNA repair in the RANBP1 high-expression phenotype. By using ssGSEA analysis, the increased RANBP1 expression was positively linked to the immune infiltration level of T helper cell type-1 (Th1) and negatively linked to the immune infiltration levels of T helper cell type-17 (Th17). Findings suggest that RANBP1 may play a pivotal role in HCC prognosis and can potentially serve as a candidate biosignature and as a therapeutic target for HCC.

The roles of risk model based on the 3-XRCC genes in lung adenocarcinoma progression.

BackgroundThe abnormal expression of deoxyribonucleic acid (DNA) repair genes might be the cause of tumor development and resistance of malignant cells to chemotherapeutic drugs. A risk model based on the X-ray repair of cross-complementary (XRCC) genes was constructed to improve the diagnosis and treatment of lung adenocarcinoma (LUAD) patients.MethodsThe expression levels, diagnostic values, and prognostic values of XRCC genes were identified, and the roles and regulatory mechanisms of the risk model based on the XRCC4/5/6 in LUAD progression was explored via The Cancer Genome Atlas (TCGA) and Oncomine databases.ResultsXRCC1/2/3/4/5/6, XRCC7 (PRKDC), and XRCC9 (FANCG) were overexpressed, and had diagnostic value for LUAD. The XRCC genes were involved in DNA repair, and participated in the regulation of non-homologous end-joining, homologous recombination, etc. The overall survival (OS), tumor (T) stage, and survival status of patients were significantly different between the Cluster1 and Cluster2 groups. XRCC4/5/6 were independent risk factors affecting the prognosis of LUAD patients. The risk score was related to the prognosis, sex, clinical stage, T, lymph node (N), and metastasis (M) stage, as well as the survival status of LUAD patients. The clinical stage and risk score were independent risk factors for poor prognosis in LUAD patients. The risk model was involved in RNA degradation, cell cycle, basal transcription factors, DNA replication etc. The risk scores were significantly correlated with the expression levels of TGFBR1, CD160, TNFSF4, TNFRSF14, IL6R, CXCL16, TNFRSF25, TAPBP, CCL16, and CCL14.ConclusionsThe risk model based on the XRCC4/5/6 genes could predict the progression of LUAD patients.

Expression and Characterization of the Staphylococcus aureus RecA protein: A mapping of canonical functions

Recombinases are responsible for homologous recombination (HR), proper genome maintenance, and accurate deoxyribonucleic acid (DNA) duplication. Moreover, HR plays a determining role in DNA transaction processes such as DNA replication, repair, recombination, and transcription. Staphylococcus aureus, an opportunistic pathogen, usually causes respiratory infections such as sinusitis, skin infections, and food poisoning. To date, the role of the RecA gene product in S. aureus remains obscure. In this study, we attempted to map the functional properties of the RecA protein. S. aureus expresses the recA gene product in vivo upon exposure to the DNA-damaging agents, ultraviolet radiation, and methyl methanesulfonate. The recombinant purified S. aureus RecA protein displayed strong single-stranded DNA affinity compared to feeble binding to double-stranded DNA. Interestingly, the RecA protein is capable of invasion and formed displacement loops and readily performed strand-exchange activities with an oligonucleotide-based substrate. Notably, the S. aureus RecA protein hydrolyzed the DNA-dependent adenosine triphosphate and cleaved LexA, showing the conserved function of coprotease. This study provides the functional characterization of the S. aureus RecA protein and sheds light on the canonical processes of homologous recombination, which are conserved in the gram-positive foodborne pathogen S. aureus.

Nucleic Acid Tests for Clinical Translation.

Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information. Overexpressed or underexpressed as well as mutated nucleic acids have been implicated in many diseases. Therefore, nucleic acid tests (NATs) are extremely important. Inspired by intracellular DNA replication and RNA transcription, in vitro NATs have been extensively developed to improve the detection specificity, sensitivity, and simplicity. The principles of NATs can be in general classified into three categories: nucleic acid hybridization, thermal-cycle or isothermal amplification, and signal amplification. Driven by pressing needs in clinical diagnosis and prevention of infectious diseases, NATs have evolved to be a rapidly advancing field. During the past ten years, an explosive increase of research interest in both basic research and clinical translation has been witnessed. In this review, we aim to provide comprehensive coverage of the progress to analyze nucleic acids, use nucleic acids as recognition probes, construct detection devices based on nucleic acids, and utilize nucleic acids in clinical diagnosis and other important fields. We also discuss the new frontiers in the field and the challenges to be addressed.

Combinatorial library design and virtual screening of cryptolepine derivatives against topoisomerase IIA by molecular docking and DFT studies

Abstract Various computational approaches have received ever-growing role in the design of potential inhibitors of the topoisomerase 2 (TOP2A) for cancer treatment. TOP2A plays a key role in the deoxyribonucleic acid (DNA) replication before cell division and thus facilitates the growth of cells. This TOP2A function can be suppressed by targeting it with potential inhibitors in cancer cells to terminate the uncontrolled cell division. Among potential inhibitors, cryptolepine has higher selectivity along with the ability to intercalate into DNA, effectively blocking TOP2A and ceasing cell division in cancer cells. However, this compound has drawbacks of being nonspecific and possessing relatively low affinity. Therefore, a combinatorial library of 31,114 cryptolepine derivatives was designed and virtually screened by molecular docking to predict the molecular interactions between the cryptolepine derivatives and TOP2A using cryptolepine as a standard. All the binding poses of cryptolepine derivatives for TOP2A were investigated to calculate binding energy. The compounds with the database numbers 8618, 907, 147, 16755, and 8186 scored the highest binding energies, −9.88, −9.76, −9.75, −9.73, and −9.72 kcal/mol, respectively, and the highest binding affinities while the cryptolepine binding energy is −6.09 kcal/mol. The strong binding interactions of these derivatives show that they can be used as potent TOP2A inhibitors and act as more effective anticancer agents than cryptolepine itself. The interactions of these derivatives with different amino acid residues were also observed and analyzed. A comprehensive understanding of the interactions of the proposed derivatives with TOP2A helped for searching more novel and potent drug-like molecules for anticancer therapy. This computational study suggests useful references to understand inhibition mechanisms that will help in the further modifications of TOP2A inhibitors. Moreover, the DFT study of the derivatives with the highest binding energies was performed, helping to further understand the binding affinities of these compounds.

Isatin-derived azoles as new potential antimicrobial agents: Design, synthesis and biological evaluation

Novel antibiotics are forced to be developed on account of multidrug-resistant bacteria with serious threats to human health. This work developed isatin-derived azoles as new potential antimicrobial agents. Bioactive assay revealed that isatin hybridized 1,2,4-triazole 7a exhibited excellent inhibitory activity against E. coli ATCC 25,922 with an MIC value of 1 µg/mL, which was 8-fold more potent than reference drug norfloxacin. The active molecule 7a possessed the ability to kill some bacteria and fungi as well as displayed low propensity to induce resistance towards E. coli ATCC25922. Preliminary mechanism investigation indicated that hybrid 7a might block deoxyribonucleic acid (DNA) replication by intercalating with DNA and possibly interacting with DNA polymerase III, thus exerting its antimicrobial potency.

Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms.

Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner.

PprI: The Key Protein in Response to DNA Damage in Deinococcus.

Deoxyribonucleic acid (DNA) damage response (DDR) pathways are essential for maintaining the integrity of the genome when destabilized by various damaging events, such as ionizing radiation, ultraviolet light, chemical or oxidative stress, and DNA replication errors. The PprI–DdrO system is a newly identified pathway responsible for the DNA damage response in Deinococcus, in which PprI (also called IrrE) acts as a crucial component mediating the extreme resistance of these bacteria. This review describes studies about PprI sequence conservation, regulatory function, structural characteristics, biochemical activity, and hypothetical activation mechanisms as well as potential applications.

LncRNA FOXD2-AS1 knockdown inhibits the resistance of human osteosarcoma cells to cisplatin by inhibiting miR-143 expression.

The aim of this study was to explore the effect of long non-coding ribonucleic acid (lncRNA) FOXD2-adjacent opposite strand RNA 1 (FOXD2-AS1) on the sensitivity of osteosarcoma cells to cisplatin and its possible underlying mechanism. Our findings might help to provide a certain reference for clinically preventing the drug resistance of osteosarcoma cells. Cisplatin with a certain concentration gradient was used to induce the stable acquired resistance of human osteosarcoma U2-OS cell line. Subsequently, the expression level of lncRNA FOXD2-AS1 was determined in osteosarcoma cells in non-resistance group (Control group) and Cisplatin-resistance group (Cisplatin-RES group), respectively. Next, the cell line with stable lncRNA FOXD2-AS1 knockdown was constructed in Cisplatin-RES group using small interfering RNA (siRNA). The effects of stable knockdown of lncRNA FOXD2-AS1 on the proliferation of human osteosarcoma cells and the half-maximal inhibitory concentration (IC50) of cisplatin were detected by Cell Counting Kit-8 (CCK-8) assay. 5-ethynyl-2'-deoxyuridine (EdU) staining was performed to measure deoxyribonucleic acid (DNA) replication level in each group of cells. The protein expression levels of apoptosis-associated genes B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) in each group of cells were measured via Western blotting. The migration and invasion abilities of cells in each group were determined using wound-healing assay and transwell assay. In addition, the expression of micro RNA (miR)-143 in each group of cells was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Compared with Control group, the expression level of lncRNA FOXD2-AS1 rose significantly in cells in Cisplatin-RES group (p<0.05). Knockdown of FOXD2-AS1 evidently decreased the IC50 of cisplatin in human osteosarcoma cells (p<0.05). According to EdU staining results, the knockdown of FOXD2-AS1 distinctly inhibited the proliferation of osteosarcoma cells (p<0.05). Western blotting results demonstrated that the knockdown of FOXD2-AS1 remarkably upregulated the expression of pro-apoptotic protein Bax and repressed that of anti-apoptotic protein Bcl-2 in drug-resistant human osteosarcoma cells (p<0.05). Moreover, the knockdown of FOXD2-AS1 significantly weakened the migration and invasion abilities of drug-resistant human osteosarcoma cells (p<0.05). Finally, it was found that the expression level of miR-143 was distinctly elevated in drug-resistant human osteosarcoma cells after knockdown of FOXD2-AS1 (p<0.05). LncRNA FOXD2-AS1 knockdown inhibits the resistance of human osteosarcoma cells to cisplatin, promotes their apoptosis and weakens their invasion and migration abilities. The possible underlying mechanism may be related to the inhibition of miR-143 expression by lncRNA FOXD2-AS1 in drug-resistant cell lines.

Visualization of DNA Replication in Single Chromosome by Stable Isotope Labeling

Among the inheritance of cellular components during cell division, deoxyribonucleic acid (DNA) and its condensate (chromosome) are conventionally visualized using chemical tag-labeled nucleotide analogs. However, associated mutagenesis with nucleotide analogs in the visualization of chromosomes is cause for concern. This study investigated the efficiency of using stable isotope labels in visualizing the replicating cultured human cell-chromosomes, in the absence of analog labels, at a high spatial resolution of 100 nm. The distinct carbon isotope ratio between sister chromatids reflected the semi-conservative replication of individual DNA strands through cell cycles and suggested the renewal of histone molecules in daughter chromosomes. Thus, this study provides a new, powerful approach to trace and visualize cellular components with stable isotope labeling.Key words: stable isotope, chromosome replication, semi-conservative replication, imaging, mass spectrometry.

Indolo[2,3-a]carbazole Derivatives with Antitumor Activity and Instrumental Methods for Their Investigation (Review)

Introduction. Currently, more than 600 thousand people a year are affected by malignant tumors on the territory of the Russian Federation. Despite the large selection of antitumor drugs and the variety of mechanisms of their action, the effectiveness of existing drugs continues to be insufficient. The main disadvantages of most antitumor drugs are the emergence of tolerance to them of tumor cells, a limited range of action and high toxicity. In this regard, the creation of effective original domestic antitumor drugs still remains relevant. Among the numerous natural and synthetic heterocyclic compounds that exhibit antitumor activity, indolo[2,3-a]carbazole derivatives that can initiate various pathways of tumor cell death are of increasing interest. The main targets for their action are topoisomerases and protein kinases, which play an important role in the processes of replication, transcription, repair or recombination of deoxyribonucleic acid (DNA). Due to this, in addition to antitumor activity, this group of compounds shows antibacterial, аntiprotozoal and immunomodulatory activity, which makes them a very promising class of candidates for the creation of new drugs.Text. The purpose of this review is to discuss instrumental methods for qualitative and quantitative analysis of indolo[2,3-a]carbazole derivatives used in the world's leading pharmacopoeias. These methods can be used both in pharmacokinetic studies, and in the standardization of these compounds, in the form of pharmaceutical substances, or as part of drug forms.Conclusion. To further introduce a new group of antitumor drugs based on indole[2,3-a]carbazole derivatives into medical practice, a deep and thorough study of their physical and chemical properties is necessary. Justification and development of analysis methods allow us to develop methods applicable to pharmacokinetic studies, as well as to create regulatory documents for quality control and standardization of indolo[2,3-a] carbazole derivatives as pharmaceutical substances. A study of the literature that describes methods for analyzing indolo[2,3-a]carbazole derivatives indicates that spectrometric (infrared and ultraviolet spectrometry) and chromatographic (thin-layer chromatography and high-performance liquid chromatography) methods are most often used to determine the authenticity and quantitative analysis of these compounds.

Recent Advances in Zinc Oxide Nanostructures with Antimicrobial Activities.

This article reviews the recent developments in the synthesis, antibacterial activity, and visible-light photocatalytic bacterial inactivation of nano-zinc oxide. Polycrystalline wurtzite ZnO nanostructures with a hexagonal lattice having different shapes can be synthesized by means of vapor-, liquid-, and solid-phase processing techniques. Among these, ZnO hierarchical nanostructures prepared from the liquid phase route are commonly used for antimicrobial activity. In particular, plant extract-mediated biosynthesis is a single step process for preparing nano-ZnO without using surfactants and toxic chemicals. The phytochemical molecules of natural plant extracts are attractive agents for reducing and stabilizing zinc ions of zinc salt precursors to form green ZnO nanostructures. The peel extracts of certain citrus fruits like grapefruits, lemons and oranges, acting as excellent chelating agents for zinc ions. Furthermore, phytochemicals of the plant extracts capped on ZnO nanomaterials are very effective for killing various bacterial strains, leading to low minimum inhibitory concentration (MIC) values. Bioactive phytocompounds from green ZnO also inhibit hemolysis of Staphylococcus aureus infected red blood cells and inflammatory activity of mammalian immune system. In general, three mechanisms have been adopted to explain bactericidal activity of ZnO nanomaterials, including direct contact killing, reactive oxygen species (ROS) production, and released zinc ion inactivation. These toxic effects lead to the destruction of bacterial membrane, denaturation of enzyme, inhibition of cellular respiration and deoxyribonucleic acid replication, causing leakage of the cytoplasmic content and eventual cell death. Meanwhile, antimicrobial activity of doped and modified ZnO nanomaterials under visible light can be attributed to photogeneration of ROS on their surfaces. Thus particular attention is paid to the design and synthesis of visible light-activated ZnO photocatalysts with antibacterial properties

An overview of high-mobility group box 1, a potent pro-inflammatory cytokine in asthma.

High-mobility group box 1 (HMGB1), also called amphoterin, HMG1 and p30, is a highly conserved protein between different species that has various functions in nucleus such as stabilization of nucleosome formation, facilitation of deoxyribonucleic acid (DNA) bending and increasing the DNA transcription, replication and repair. It has also been indicated that HMGB1 acts as a potent pro-inflammatory cytokine with increasing concentrations in acute and chronic inflammatory diseases. Asthma is a common chronic respiratory disease associated with high morbidity and mortality rates. One central characteristic in its pathogenesis is airway inflammation. Considering the inflammatory role of HMGB1 and importance of inflammation in asthma pathogenesis, a better understanding of this protein is vital. This review describes the structure, cell surface receptors, signaling pathways and intracellular and extracellular functions of HMGB1, but also focuses on its inflammatory role in asthma. Moreover, this manuscript reviews experimental and clinical studies that investigated the pathologic role of HMGB1.

Identification of differentially expressed microRNAs of sunflower seedlings under drought stress

AbstractSunflower (Helianthus annuus L.) is considered to be drought‐tolerant, the roles of microribonucleic acids (miRNAs) in the response to drought have not been thoroughly studied. In this work, differentially expressed miRNAs of sunflower seedlings under drought stress were identified, and putative target genes were predicted. Ultimately, 163 known miRNAs and 90 novel miRNAs were identified and discovered. Under drought stress, 54 and 25 miRNAs were up‐regulated and down‐regulated in leaves, while 94 and 10 miRNAs were up‐regulated and down‐regulated in roots, respectively. A total of 1788 target genes were predicted. The results of gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of target genes indicated that 47 and 74 genes were enriched for 14 and 19 GO terms in leaves and roots, respectively. In leaf, seven genes were possibly associated with binding to meta lion, adenyl ribonucleotide, alcohol and protein, two genes with transferase activity, three genes with hormone responses, and two genes with hormone‐mediated signaling pathways. In root, 23 genes were associated with binding functions, two genes with lignin metabolic processes, and three genes with hormone responses. We also discovered 40 target genes related to spliceosome function, of which three genes may take part in deoxyribonucleic acid (DNA) replication pathways that include nucleotide excision repair, mismatch repair, and homologous recombination. Sequencing of miRNAs and digital expression spectrum demonstrated that the differential expression of 21 genes may be the results of miRNAs regulating. These findings provide new information regarding molecular mechanisms of sunflower drought responses and add to the number of plant drought tolerance genes.