National Center For Biotechnology Research Articles

Molecular Detectıon of Canine Leishmaniasis in Northern Anatolia, Turkiye.

Canin leishmaniasis (CanL), mostly caused by Leishmania infantum, is one of the most important vector-borne diseases in dogs in the Mediterranean region. In this study, we aimed to determine the disease profile in this region by firstly making microscopic and then molecular analyzes in the samples taken from the dogs. Overall, 112 whole blood samples taken from dogs for clinical applications by a veterinarian in Cankırı between December 2021 and November 2022 were used. After blood collection, both thin and thick drop blood smear preparations were prepared and evaluated for Giemsa staining. L. infantum was investigated by Real time-PCR (RT-PCR) method from all blood samples. Sequence analysis and phylogenetic tree study were performed on positive samples. Both microscopic and RT-PCR analyzes were performed. In both studies, 3 of the 112 samples were positive. Because of the sequence analysis, they were L. infantum. Sequence analysis was performed from the samples found 3 positive. The phylogenetic tree was drawn by making NCBI (National Center for Biotechnology) data entries of the positive samples (Accession numbers: OQ184728, OQ184729, OQ184730). Dogs are important, as they are reservoir of this disease. In this study, 3 (2.7%) positive Leishmaniasis was detected in dogs in Cankırı. Ultimately, this should prompt discussion about new strategies going forward to combat infection caused by Leishmania.

Candida albicans and Antifungal Peptides.

Candida albicans, a ubiquitous opportunistic fungal pathogen, plays a pivotal role in human health and disease. As a commensal organism, it normally resides harmlessly within the human microbiota. However, under certain conditions, C.albicans can transition into a pathogenic state, leading to various infections collectively known as candidiasis. With the increasing prevalence of immunocompromised individuals and the widespread use of invasive medical procedures, candidiasis has become a significant public health concern. The emergence of drug-resistant strains further complicates treatment options, highlighting the urgent need for alternative therapeutic strategies. Antifungal peptides (AFPs) have gained considerable attention as potential candidates for combating Candida spp. infections. These naturally occurring peptides possess broad-spectrum antimicrobial activity, including specific efficacy against C.albicans. AFPs exhibit several advantageous properties, such as rapid killing kinetics, low propensity for resistance development, and diverse mechanisms of action, making them promising alternatives to conventional antifungal agents. In recent years, extensive research has focused on discovering and developing novel AFPs with improved efficacy and selectivity against Candida species. Advances in biotechnology and synthetic peptide design have enabled the modification and optimization of natural peptides, enhancing their stability, bioavailability, and therapeutic potential. Nevertheless, several challenges must be addressed before AFPs can be widely implemented in clinical practice. These include optimizing peptide stability, enhancing delivery methods, overcoming potential toxicity concerns, and conducting comprehensive preclinical and clinical studies. This commentary presents a short overview of candidemia and AFP; articles and reviews published in the last 10years were searched on The National Library of Medicine (National Center for Biotechnology Information-NIH-PubMed). The terms used were C.albicans infections, antimicrobial peptides, antifungal peptides, antifungal peptides mechanisms of action, candidemia treatments and guidelines, synthetic peptides and their challenges, and antimicrobial peptides in clinical trials as the main ones. Older publications were cited if they brought some relevant concept or helped to bring a perspective into our narrative. Articles older than 20years and those that appeared in PubMed but did not match our goal to bring updated information about using antifungal peptides as an alternative to C.albicans infections were not considered.

Diagnosis of two local mushroom species (Pleurotus spp.) and their production management

The present study confirmed the identity of two Iraqi mushrooms by using the internal transcribed spacer (ITS) sequence; the genomic DNA of two isolates was amplified using ITS1 and ITS4 primers, and the data analyzed through Basic Local Alignment Tool( BLAST) search was achieved using the National Center for Biotechnology Information (NCBI) database. The result shows that the nucleotide sequence of two mushrooms blasted against the sequence from the Gene Bank database that Pleurotus ostreatus and Pleurotus eryngii matched 99% and 100%, respectively. The second stage of the current study was the comparison of different agro-waste, including wheat straw(WS), corncob(CC) and sawdust(SD) supplemented with 25% wheat bran(W) and 2% calcium carbonate (CaCo3) on mycelium growth, yield and biological efficiency (BE) of local oyster mushroom which comparison with Chinese strain pleurotus ostreatus121 and pleurotus eryngii 080. The highest growth average of local P. ostretus on the SD substrate was 1.50 cm, and P.eryngii was recorded at 1.18 cm. The substrate CC was the most suitable for the yield of mushroom local P. ostreatus and P. ostreatus121(485.40 and 418.50 g/bag, respectively), while local P. eryngii recorded 470.40 in the same substrate. It was also found that the WS substrate recorded the highest BE for each local isolate and Chinese strain. Keywords: Iraqi strains, Pleurotus spp., agricultural wastes, wild agricultural mushrooms

GENETIC ANALYSIS AND MOLECULAR CHARACTERIZATION OF THE WHEATGRASS (AGROPYRON CRISTATUM L. GAERTN.) IN SOUTH-EAST KAZAKHSTAN

Assembly, genetic analysis, and preservation of wheatgrass (Agropyron cristatum L. Gaertn.) diversity is an important task in improving the said crop under the environmental conditions of the Republic of Kazakhstan. The presented study evaluated and isolated various wheatgrass species and their populations for breeding and developing promising cultivars based on the genetic principles to improve the degraded pasture situation in South-East Kazakhstan from the perspective of global climate change. For the succeeding investigations, collection of the wheatgrass landraces from various regions of Kazakhstan ensued, as well as from accessions already conserved in the gene pool, and gained evaluation under the environmental conditions of South-East Kazakhstan. In performance-based screening, 20 wheatgrass cultivars identified underwent further genotyping by using inter-simple sequence repeat (ISSRs) polymerase chain reaction markers. The pertinent study significantly contributes to understanding the Agropyron species’ genetic structure and molecular characteristics. Using seven ISSR primers helped study the kinship and genetic polymorphism of the five Agropyron species collected from diverse locations. The ISSR primers were extremely informative for determining the Agropyron’s genetic diversity and interspecific similarity. Moreover, they come highly recommended for an in-depth study comparing the DNA sequencing of the Agropyron populations available in the National Center for Biotechnology’s database.

DEVELOPMENT OF A TECHNOLOGY FOR OBTAINING A PROBIOTIC STRAIN LACTOBACILLUS BULGARICUS C-2, PROMISING FOR THE PRODUCTION OF STARTER CULTURES AND BIOLOGICALLY ACTIVE ADDITIVES

Lactic acid probiotic bacteria can be widely used for the prevention and treatment of patients with various diseases, such as acute and chronic diseases of the gastrointestinal tract, respiratory tract, to restore intestinal microbiocenosis, in combination with antibiotic therapy. The form of intake of these microorganisms is diverse: fermented milk products, drugs, dietary supplements. In the production of lactic acid starters, including the probiotic strain Lactobacillus bulgaricus, there are problems in the selection of nutrient media and conditions for deep cultivation, the selection of methods and conditions for concentration, and the selection of cryoprotectants for freeze drying. This article presents all the data for the production of the Lactobacillus bulgaricus C-2 strain in powder form with the maximum yield of microorganism cells, promising for introduction into the composition of starter cultures for the dairy industry and into biologically active additives with a probiotic effect. The Lactobacillus bulgaricus C-2 strain was isolated from koumiss and stored in the collection of the branch of the Republican State Enterprise on the REM of the Ministry of Health of the Republic of Kazakhstan "National Center for Biotechnology" in Stepnogorsk. The production nutrient medium, conditions for deep cultivation, methods and conditions of concentration were selected, optimal cryoprotectants for freeze-drying were selected.

Characteristics of alanine racemase in Lactobacillus sakeiZH-2 strain.

Some d-amino acid functions for food production are widely known: d-alanine improves sensory evaluations of sake, beer, and fermented foods. Therefore, for the application of d-amino acids, alanine racemase (ALRase) in Lactobacillus sakei ZH-2, which has strong racemization, was analyzed using molecular biological methods. It had been hypothesized that ALRase coding DNA, alr, in ZH-2 strain differs from those of other Lactobacillus sakei strains. However, complete genome sequencing by the National Center for Biotechnology (NCBI) revealed the amino acid sequence of alr in ZH-2 strain to have homology of 99.4% similarity with the alr in Lactobacillus sakei 23K strain. However, it is considered that the sequence of alr was a unique amino acid sequence in the lactic acid bacteria group. DNA "alr" of ZH-2 strain has a 1140 bp DNA base with 41 kDa molecular mass. Its molecular mass was inferred as approximately 38.0 kDa using SDS-PAGE. Its optimum conditions are pH 9.0 at 30-40°C, showing stability at pH 9.0-10.0 and 4-40°C. Its cofactor is pyridoxal phosphate. Its activity is activated more by copper and zinc ions than by the lack of a metal ion. Additionally, its K m is 1.32 × 10-3 (mol), with V max of 4.27 × 10-5 (μmol-1 min-1). ALRase reacted against alanine most strongly in other substrates such as amino acids. The enzyme against serine was found to have 40% activity against alanine. The enzyme converted up to 54.5% of d-alanine from l-alanine ZH-2 strain.

ElasticBLAST: accelerating sequence search via cloud computing

BackgroundBiomedical researchers use alignments produced by BLAST (Basic Local Alignment Search Tool) to categorize their query sequences. Producing such alignments is an essential bioinformatics task that is well suited for the cloud. The cloud can perform many calculations quickly as well as store and access large volumes of data. Bioinformaticians can also use it to collaborate with other researchers, sharing their results, datasets and even their pipelines on a common platform.ResultsWe present ElasticBLAST, a cloud native application to perform BLAST alignments in the cloud. ElasticBLAST can handle anywhere from a few to many thousands of queries and run the searches on thousands of virtual CPUs (if desired), deleting resources when it is done. It uses cloud native tools for orchestration and can request discounted instances, lowering cloud costs for users. It is supported on Amazon Web Services and Google Cloud Platform. It can search BLAST databases that are user provided or from the National Center for Biotechnology Information.ConclusionWe show that ElasticBLAST is a useful application that can efficiently perform BLAST searches for the user in the cloud, demonstrating that with two examples. At the same time, it hides much of the complexity of working in the cloud, lowering the threshold to move work to the cloud.

Cannabis and Sleep: A Systematic Review of the Effects of Cannabinoids on Sleep Disorders

Introduction: Sleep disorders are a common problem in society in the modern world. Patients are increasingly seeking alternative treatments for insomnia in order to reduce the side effects of prescription drugs. A new trend is the use of cannabinoids contained in cannabis plants to treat sleep disorders, making patients looking for a solution to their problem more and more eager.Aim of the study: The purpose of this paper is to present contemporary knowledge of the therapeutic benefits of cannabis compounds in treating sleep disorders and improving sleep parameters. Materials and methods: The National Center for Biotechnology Information/PubMed and Google Scholar medical databases were comprehensively analyzed by entering the keywords: cannabis, sleep disorders, insomnia, cannabinoids, THC, CBD in their respective configurations. Analyzing the searched literature, data from 18 scientific articles from the last five years (2017-2022) were evaluated.Results: Cannabinoids may have benefits in sleep-related disorders. The literature does not agree on the effectiveness of their use in treating sleep disorders. The highly variable availability of cannabinoid formulations on the market makes it difficult to develop appropriate dosages for the treatment of insomnia.Conclusions: Research on cannabis and sleep is in its early stages and needs to be continued in order to improve knowledge. There is a need for further long-term studies that are rigorously controlled and use larger study groups.

Application of gabapentinoids and novel compounds for the treatment of benzodiazepine dependence: the glutamatergic model.

Current approaches for managing benzodiazepine (BZD) withdrawal symptoms are daunting for clinicians and patients, warranting novel treatment and management strategies. This review discusses the pharmacodynamic properties of BZDs, gabapentinoids (GBPs), endozepines, and novel GABAergic compounds associated with potential clinical benefits for BZD-dependent patients. The objective of this study was to review the complex neuromolecular changes occurring within the GABAergic and glutamatergic systems during the BZD tolerance and withdrawal periods while also examining the mechanism by which GBPs and alternative pharmacological therapies may attenuate withdrawal symptoms. An elaborative literature review was conducted using multiple platforms, including the National Center for Biotechnology (NCBI), AccessMedicine, ScienceDirect, pharmacology textbooks, clinical trial data, case reports, and PubChem. Our literature analysis revealed that many distinctive neuroadaptive mechanisms are involved in the GABAergic and glutamatergic systems during BZD tolerance and withdrawal. Based on this data, we hypothesize that GBPs may attenuate the overactive glutamatergic system during the withdrawal phase by an indirect presynaptic glutamatergic mechanism dependent on the α2δ1 subunit expression. GBPs may benefit individuals undergoing BZD withdrawal, given that the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor current significantly increases during abrupt BZD withdrawal in animal studies. This may be a conceivable explanation for the effectiveness of GBPs in treating both alcohol withdrawal symptoms and BZD withdrawal symptoms in some recent studies. Finally, natural and synthetic GABAergic compounds with unique pharmacodynamic properties were found to exert potential clinical benefits as BZD substitutes in animal studies, though human studies are lacking.

GeneToList: A Web Application to Assist with Gene Identifiers for the Non-Bioinformatics-Savvy Scientist.

Simple SummaryWith the increasing popularity of omics technologies, many scientists are dealing with large sets of genomic data for the first time. While there are many amazing bioinformatics tools available to help analyze this data, one common difficulty these scientists face is that not all gene data or analysis tools use the same genomic nomenclature. Another issue is that many publications still use obsolete or colloquial gene aliases instead of official gene identifiers. Common gene ID conversion tools and other downstream analysis software struggle with these gene aliases. Therefore, we developed a free and publicly available web application, GeneToList, to assist in gene ID disambiguation and gene ID conversion, with a specific focus on a user-friendly interface for the non-bioinformatics-savvy scientist.The increasing incorporation of omics technologies into biomedical research and translational medicine presents challenges to end users of the large and complex datasets that are generated by these methods. A particular challenge in genomics is that the nomenclature for genes is not uniform between large genomic databases or between commonly used genetic analysis tools. Furthermore, outdated genomic nomenclature can still be found amongst scientific communications, including peer-reviewed manuscripts. Therefore, a web application (GeneToList) was developed to assist in gene ID conversion and alias matching, with a specific focus on achieving a user-friendly interface for the non-bioinformatics-savvy scientist. It currently includes gene information for over 38,000 different taxa retrieved from the National Center for Biotechnology and Information (NCBI) Gene resource. Supported databases of gene IDs include NCBI Gene Symbols, NCBI Gene IDs (Entrez IDs), OMIM IDs, HGNC IDs, Ensembl IDs, and 28 other taxa-specific identifiers. GeneToList is available at genetolist.com. The tool is a web application that is compatible with many standard browsers. The gene ID conversion feature of this application was found to outcompete the common gene ID conversion tools. Specifically, it was able to successfully convert all tested IDs, whereas the others were not able to recognize the gene aliases. Therefore, the gene ID disambiguation provided by this application should be beneficial for many scientists dealing with gene data when the uniformity of gene nomenclature is important for downstream analysis.

Use molecular method to detect the screw worm fly in Al-Diwaniyah province

Chrysomya bezziana this study was carried out between October, 2021 to March 31, 2022 in six region from Al-Diwaniyah province. Observe the influence of the month and type of animal on the region's. The total number of animals infected was 33 (1) cattle, (7) lambs, and (35) sheep. Al-muhnawa had the highest rate of infestation, while Al-hamza had the lowest rate of infestation. The highest rate of infestation recorded in March ()% and the lowest in February ()%.Conventional PCR (Polymerase Chain Reaction) was used for molecular identification. A DNA extraction was performed on 50 randomly chosen larvae from the total population. The size of the PCR product (548 pb) For Chrysomya bezziana, from the infected animals larvae were taken to DNA extracted and used following targeting 16S rRNA gene product size (548 bp). There follows sequence analysis to obtain the nucleotide (16S rRNA) gene, and the sequence was recoded in the National Center for Biotechnology (NCBI) with accession numbers (ON059979, ON059980, ON059981, ON059982, ON059983, ON059984, ON059985)Iraq. This gene's homology sequence identity percentage was calculated by comparing it to another globally registered gene (NCBI).

Word2vec neural model-based technique to generate protein vectors for combating COVID-19: a machine learning approach.

The world was ambushed in 2019 by the COVID-19 virus which affected the health, economy, and lifestyle of individuals worldwide. One way of combating such a public health concern is by using appropriate, rapid, and unbiased diagnostic tools for quick detection of infected people. However, a current dearth of bioinformatics tools necessitates modeling studies to help diagnose COVID-19 cases. Molecular-based methods such as the real-time reverse transcription polymerase chain reaction (rRT-PCR) for detecting COVID-19 is time consuming and prone to contamination. Modern bioinformatics tools have made it possible to create large databases of protein sequences of various diseases, apply data mining techniques, and accurately diagnose diseases. However, the current sequence alignment tools that use these databases are not able to detect novel COVID-19 viral sequences due to high sequence dissimilarity. The objective of this study, therefore, was to develop models that can accurately classify COVID-19 viral sequences rapidly using protein vectors generated by neural word embedding technique. Five machine learning models; K nearest neighbor regression (KNN), support vector machine (SVM), random forest (RF), Linear discriminant analysis (LDA), and Logistic regression were developed using datasets from the National Center for Biotechnology. Our results suggest, the RF model performed better than all other models on the training dataset with 99% accuracy score and 99.5% accuracy on the testing dataset. The implication of this study is that, rapid detection of the COVID-19 virus in suspected cases could potentially save lives as less time will be needed to ascertain the status of a patient.

Lessons learned in virulence factor identification and data management from a hackathon on microbial virulence

Virulence is a complex mix of microbial traits and host susceptibility that could ultimately lead to disease. The increased prevalence of multidrug resistant infections complicates treatment options, augmenting the need for developing robust computational methods and pipelines that enable researchers and clinicians to rapidly identify the underlying mechanism(s) of virulence in any given sample/isolate. Consequently, the National Center for Biotechnology and Information at the National Institutes of Health hosted an in-person hackathon in Bethesda, Maryland during July 2019 to assist with developing cloud-based methods to reduce reliance on local computational infrastructure. Groups of attendees were assigned tasks that are relevant to identifying relevant tools, constructing pipelines capable of identifying microbial virulence factors, and managing the associated data and metadata. Specifically, the assigned tasks consisted of the following: data indexing, metabolic functions, virulence factors, antimicrobial resistance, mobile elements in enterococci, and metatranscriptomics. The cloud-based framework established by this hackathon can be augmented and built upon by the research community to aid in the rapid identification of microbial virulence factors.

Ear Foreign Body Extraction

Ear foreign body removal is a common procedure performed in the emergency department that can happen to anyone, both children and adults. The method used in writing this literature review is a literature review. Article writing consists of several sources originating from journals and related agency guidelines. Source searches were conducted on online portals for journal publications such as Medscape, Research gate and the National Center for Biotechnology Information/NCBI (ncbi.nlm.nih.gov), with the keyword used being “ear foreign body”. Various kinds of foreign objects have been reported to have entered the ear canal including insects, beads, paper and so on. Foreign body removal techniques consist of manual instrumental, irrigation, and suctioning. Removal of foreign bodies should not be performed if the patient is suspected of having a perforation of the tympanic membrane. Removal of a foreign body from the ear canal depends on the type of foreign body present in the ear canal.

Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis.

Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies. We employed a Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis using the National Center for Biotechnology's (NCBI) Gene Expression Omnibus (GEO) to define NPC pathogenesis. We identified 111 tumor samples and 43 healthy nasopharyngeal epithelium samples from NPC public patient data. We analyzed associated signatures in Ingenuity Pathway Analysis (IPA), restricting genes that showed statistical significance (p<0.05) and an absolute experimental log ratio greater than 0.15 between disease and control samples. Our meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. Additionally, interleukin-1 (IL-1) and SB203580 were the top upstream regulators. Tumorigenesis-related genes such as homeobox A10 (HOXA10) and prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) as well as those associated with extracellular matrix degradation, such as matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) were also upregulated. Decreased expression of genes that encode proteins associated with maintaining healthy nasal respiratory epithelium structural integrity, including sentan-cilia apical structure protein (SNTN) and lactotransferrin (LTF) was documented. Importantly, we found that etanercept inhibits targets upregulated in NPC and LPS induction, such as MMP-1, PTGS2, and possibly MMP-3. Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage.

In-silico study to identify the pathogenic single nucleotide polymorphisms in the coding region of CDKN2A gene

Background: CDKN2A, encoding two important tumor suppressor proteins p16 and p14, is a tumor suppressor gene. Mutations in this gene and subsequently the defect in p16 and p14 proteins lead to the downregulation of RB1/p53 and cancer malignancy. To identify the structural and functional effects of mutations, various powerful bioinformatics tools are available. The aim of this study is the identification of high-risk non-synonymous single nucleotide variants in the CDKN2A gene via bioinformatics tools.&#x0D; Materials and Methods: Among the identified polymorphisms in this gene, 353 missense variants are retrieved from the national center for biotechnology information/single nucleotide polymorphism database (NCBI/dbSNP). Then, the pathogenicity of missense variants are considered using different bioinformatics tools. The stability of these mutant proteins, conservation of amino acids and the secondary and tertiary structural changes are analyzed by bioinformatics tools. After the identification of high-risk mutations, the changes in the hydrophobicity of high-risk amino acid substitutions are considered.&#x0D; Results: Deleterious single nucleotide polymorphisms (SNPs) were screened step by step using the bioinformatics tools. The results obtained from the set of bioinformatics tools identify high-risk mutations in CDKN2A gene.&#x0D; Conclusion: 18 high-risk mutations including L16R/Q, G23D/R/S, L32P, N42K, G55D, G67D/R, P81R, H83R, G89D/S, A102E, G101R, G122R, and V126D were identified. According to the previous experimental studies, the association of L16R, G23D/R/S, L32P, G67R, H83R, G89D, G101R, and V126D amino acid substitutions with various cancers has been confirmed.

In Silico Analysis of Common Long Noncoding RNAs in Schistosoma mansoni and Schistosoma haematobium.

Background Schistosomiasis caused by Schistosoma parasites is one of the most common parasitic infections worldwide. Genetic regulation of the genus Schistosoma, which has different developmental stages throughout its life, is quite complex. In these parasites, thousands of long noncoding RNAs (lncRNAs) estimated to be functional were identified. Identifying the transcripts expressed in common and detecting their functions for better understanding of the role of these lncRNAs require a comparative study. Methods Assembled RNA-seq datasets belonging to S. mansoni and S. haematobium were obtained from the National Center for Biotechnology. A basic local alignment search tool (BLASTN) analysis was conducted against previously constructed lncRNA library to identify the common lncRNAs between two species. LncRNAs target genes and their gene ontology annotation was performed. Results In S. mansoni and S. haematobium, 5132 and 3589 lncRNA transcripts were detected, respectively. These two species had 694 lncRNAs in common. A significant number of lncRNAs was determined to be transcribed from sex chromosomes. The frequently expressed lncRNAs appear to be involved in metabolic and biological regulation processes. Conclusions These two species share similar lncRNAs; thus, this finding is a clue that they might have similar functions. In sexual development, they especially might play important roles. Our results will provide important clues to further studies about interactions between human hosts and parasites and the infection mechanisms of Schistosoma parasites.

MiR-193a-3p Promotes the Invasion, Migration, and Mesenchymal Transition in Glioma through Regulating BTRC.

Background The present study is aimed at exploring the specific expression of miR-193a-3p and the mechanism underlying miR-193a-3p-mediated mesenchymal transition (MT), invasion, and migration in glioma. Methods The gene expression profile datasets of GSE39486 and GSE25676 were downloaded from the National Center for Biotechnology (NCBI). Data regarding the expression of miR-193a-3p and survival curves were derived from Chinese Glioma Genome Atlas (CGGA). Online websites including miRWalk, DIANA, and starbase were employed to predict the target genes for miR-193a-3p. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by the Omicsbean online software. Module analysis of the protein-protein interaction (PPI) networks was performed by the plug-in Molecular Complex Detection (MCODE), and the degrees of genes were calculated by CytoHubba plug-in of Cytoscape. Survival curves were based on the Gene Expression Profile Interaction Analysis (GEPIA). Transwell, wound healing, and Western blot experiments were performed to investigate the effects of miR-193a-3p and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) on the invasion, migration, and MT of glioma. Results miR-193a-3p was highly expressed in glioma tissues and significantly correlated with poor survival in patients with glioma. The target genes for miR-193a-3p were involved in many cancer-related signaling pathways. The PPI showed 11 genes with both high degrees and MCODE scores in the network. Survival analysis demonstrated that the expression of BTRC was significantly correlated with the prognosis of patients with glioma. The results from the transwell, wound healing, and Western blot analyses suggested that miR-193a-3p promoted the invasion, migration, and MT of glioma cells, which could be reversed by BTRC. Conclusions miR-193a-3p was upregulated in patients with glioma and could affect the invasion, migration, and MT of glioma by regulating BTRC.

Rivaroxaban for the treatment of venous thromboembolism in pediatric patients

ABSTRACT Introduction Anticoagulant therapy is in use for both prevention and treatment of venous and arterial thromboembolic disorders. Delivering safe and effective anticoagulation in the pediatric population is challenging, since the available standard therapy with parenteral UFH and LMWH is troublesome for most pediatric patients, and VKAs require frequent INR monitoring due to the unpredictable pharmacokinetics and numerous food and drug interactions. Rivaroxaban, a direct FXa inhibitor, offers the convenience of oral administration and predictable pharmacokinetics across a wide range of patients. Its safety and efficacy have been previously established in various adult indications. Areas covered This review outlines pharmacologic and clinical aspects regarding rivaroxaban treatment in adults and children, and provides a broad appraisal of the The EINSTEIN-Jr program which evaluated the safety and efficacy of body-weight adjusted pediatric rivaroxaban regimens for the treatment of VTE in children. A review of the literature using the keywords rivaroxaban and pediatric venous thromboembolism was conducted within the National Center for Biotechnology (NCBI) and EMBASE databases. Expert opinion Rivaroxaban represents an appealing therapeutic alternative for VTE in children. Further research should explore additional indications for rivaroxaban in the pediatric population beyond that of VTE.

Aldehyde dehydrogenase 2 protects against abdominal aortic aneurysm formation by reducing reactive oxygen species, vascular inflammation, and apoptosis of vascular smooth muscle cells

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies aldehydes by converting them to carboxylic acids. ALDH2 deficiency is known to increase oxidative stress. Increased oxidative stress plays a pivotal role in abdominal aortic aneurysm (AAA) pathogenesis. Reactive oxygen species (ROS) promote degradation of the extracellular matrix (ECM) and vascular smooth muscle cell (VSMC) apoptosis. Reducing oxidative stress by an ALDH2 activator could have therapeutic potential for limiting AAA development. We hypothesized that ALDH2 deficiency could increase the risk for AAA by decreasing ROS elimination and that an ALDH2 activator could provide an alternative option for AAA treatment. The National Center for Biotechnology (NCBI) Gene Expression Omnibus (GEO) database was used. Human aortic smooth muscle cells (HASMCs) were used for the in vitro experiments. Gene-targeted ALDH2*2 KI knock-in mice on a C57BL/6J background and apolipoprotein E knockout (ApoE KO) mice were obtained. An animal model of AAA was constructed using osmotic minipumps to deliver 1000ng/kg/min angiotensin II (AngII) for 28days. Patients with AAA had significantly lower ALDH2 expression levels than normal subjects. ALDH2*2 KI mice were susceptible to AngII administration, exhibiting significantly increased AAA incidence rates and increased aortic diameters. Alda-1, an ALDH2 activator, reduced AngII-induced ROS production, NF-kB activation, and apoptosis in HASMCs. Alda-1 attenuated AngII-induced aneurysm formation and decreased aortic expansion in ApoE KO mice. We concluded that ALDH2 deficiency is associated with the development of AAAs in humans and a murine disease model. ALDH2 deficiency increases susceptibility to AngII-induced AAA formation by attenuating anti-ROS effects and increasing VSMC apoptosis and vascular inflammation. Alda-1 was shown to attenuate the progression of experimental AAA in a murine model.