Identification Of Molecular Markers Research Articles

ATP-Binding Cassette Subfamily G Member 2 in Acute Myeloid Leukemia: A New Molecular Target?

Despite the progress in the knowledge of disease pathogenesis and the identification of many molecular markers as potential targets of new therapies, the cure of acute myeloid leukemia remains challenging. Disease recurrence after an initial response and the development of resistance to old and new therapies account for the poor survival rate and still make allogeneic stem cell transplantation the only curative option. Multidrug resistance (MDR) is a multifactorial phenomenon resulting from host-related characteristics and leukemia factors. Among these, the overexpression of membrane drug transporter proteins belonging to the ABC (ATP-Binding Cassette)-protein superfamily, which diverts drugs from their cellular targets, plays an important role. Moreover, a better understanding of leukemia biology has highlighted that, at least in cancer, ABC protein's role goes beyond simple drug transport and affects many other cell functions. In this paper, we summarized the current knowledge of ABCG2 (formerly Breast Cancer Resistance Protein, BCRP) in acute myeloid leukemia and discuss the potential ways to overcome its efflux function and to revert its ability to confer stemness to leukemia cells, favoring the persistence of leukemia progenitors in the bone marrow niche and justifying relapse also after therapy intensification with allogeneic stem cell transplantation.

Analysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity

Inhibition of angiogenesis is an important mode of action for the teratogenic effect of chemicals and drugs. There is a gap in the availability of simple, experimental screening models for the detection of angiogenesis inhibition. The zebrafish embryo represents an alternative test system which offers the complexity of developmental differentiation of an entire organism while allowing for small-scale and high-throughput screening. Here we present a novel automated imaging-based method to detect the inhibition of angiogenesis in early life stage zebrafish. Video subtraction was used to identify the location and number of functional intersegmental vessels according to the detection of moving blood cells. By exposing embryos to multiple tyrosine kinase inhibitors including SU4312, SU5416, Sorafenib, or PTK787, we confirmed that this method can detect concentration-dependent inhibition of angiogenesis. Parallel assessment of arterial and venal aorta ruled out a potential bias by impaired heart or blood cell development. In contrast, the histone deacetylase inhibitor valproic acid did not affect ISV formation supporting the specificity of the angiogenic effects. The new test method showed higher sensitivity, i.e. lower effect concentrations, relative to a fluorescent reporter gene strain (Tg(KDR:EGFP)) exposed to the same tyrosine kinase inhibitors indicating that functional effects due to altered tubulogenesis or blood transport can be detected before structural changes of the endothelium are visible by fluorescence imaging. Comparison of exposure windows indicated higher specificity for angiogenesis when exposure started at later embryonic stages (24 h post-fertilization). One of the test compounds was showing particularly high specificity for angiogenesis effects (SU4312) and was, therefore, suggested as a model compound for the identification of molecular markers of angiogenic disruption. Our findings establish video imaging in wild-type strains as viable, non-invasive, high-throughput method for the detection of chemical-induced angiogenic disruption in zebrafish embryos.

Clinical and molecular characterisation of metastatic papillary thyroid cancer according to radioiodine therapy outcomes.

Radioiodine (RAI) therapy remains the gold-standard approach for distant metastatic differentiated thyroid cancer (TC). The main objective of our work was to identify the clinical and molecular markers that may help to predict RAI avidity and RAI therapy response of metastatic lesions in a cohort of papillary thyroid cancer (PTC) patients. We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre. The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients' primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively). Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies.

Genome-wide association study of growth traits and validation of key mutations (MSTN c.C861T) associated with the muscle mass of meat pigeons.

Selective breeding of meat pigeons is primarily based on growth traits, especially muscle mass (MM). Identification of functional genes and molecular markers of growth and slaughter traits through a genome-wide association study (GWAS) will help to elucidate the underlying molecular mechanisms and provide a theoretical basis for the selective breeding of meat pigeons. The phenotypic data of body weight (BW) and body size (BS) of 556 meat pigeons at 52 and 80 weeks of age were collected. In total, 160 434 high-quality single nucleotide polymorphism sites were obtained by restriction site-associated DNA sequencing. The GWAS analysis revealed that MSTN, IGF2BP3 and NCAPG/LCORL were important candidate genes affecting the growth traits of meat pigeons. IGF2BP3 and NCAPG/LCORL were highly correlated to BW and BS, which are related to overall growth and development, while MSTN was associated with pectoral thickness and BW. Phenotypic association validation with the use of two meat pigeon populations found that the MSTN mutation c.C861T determines the MM. These results provide new insights into the genetic mechanisms underlying phenotypic variations of growth traits and MM in commercial meat pigeons. The identified markers and genes provide a theoretical basis for the selective breeding of meat pigeons.

Optical Genome Mapping as a Tool to Unveil New Molecular Findings in Hematological Patients with Complex Chromosomal Rearrangements.

Standard cytogenetic techniques (chromosomal banding analysis-CBA, and fluorescence in situ hybridization-FISH) show limits in characterizing complex chromosomal rearrangements and structural variants arising from two or more chromosomal breaks. In this study, we applied optical genome mapping (OGM) to fully characterize two cases of complex chromosomal rearrangements at high resolution. In case 1, an acute myeloid leukemia (AML) patient showing chromothripsis, OGM analysis was fully concordant with classic cytogenetic techniques and helped to better refine chromosomal breakpoints. The OGM results of case 2, a patient with non-Hodgkin lymphoma, were only partially in agreement with previous cytogenetic analyses and helped to better define clonal heterogeneity, overcoming the bias related to clonal selection due to cell culture of cytogenetic techniques. In both cases, OGM analysis led to the identification of molecular markers, helping to define the pathogenesis, classification, and prognosis of the analyzed patients. Despite extensive efforts to study hematologic diseases, standard cytogenetic methods display unsurmountable limits, while OGM is a tool that has the power to overcome these limitations and provide a cytogenetic analysis at higher resolution. As OGM also shows limits in defining regions of a repetitive nature, combining OGM with CBA to obtain a complete cytogenetic characterization would be desirable.

ENFOQUES GENÓMICOS Y TRANSCRIPTÓMICOS PARA ESTUDIAR ÁRBOLES MADERABLES: PERSPECTIVAS PARA EL ESTUDIO DE CEDRO ROJO (Cedrela odorata L.)

<p><strong>Introduction</strong>: The high-throughput genomic and transcriptomic approach has been developed and implemented to address the main challenges that the timber forestry sector faces, such as population growth, climate change, deforestation and the loss of forest ecosystem services. <strong>Objective:</strong> To carry out a bibliographic review focused on the genomes and transcriptomes of timber trees reported in the databases, with special attention to red cedar (<em>Cedrela odorata</em> L.), due to its importance as precious wood in Mexico. <strong>Methodology:</strong> A literature review was carried out, directed at studying timber trees with genomic and transcriptomic strategies in different databases such as Pubmed, Scopus, Google Scholar, ScienceDirect, Wiley Online Library, MDPI and Scielo to identify the timber species that have been reported genomes and transcriptomes. The structure of the review was the genomics of timber trees, the transcriptomics of wood, and the potential species for study due to their importance and finally, the databases for consultation. Subsequently, a bibliometric study was carried out with the bibliometrix library in R Studio. <strong>Main results</strong>: The first genome to be assembled at the chromosome level was the black cottonwood. Among the timber trees, the genomes of black cottonwood, desert poplar, eucalyptus and oak with a length of 392, 496, 691 and 789 Mb have been reported. Through study of the transcriptome, it has been possible to identify genes related to formation of the wood in a hybrid poplar (<em>Populus alba</em> L.<em> × P. glandulosa</em>) and <em>P. tremula</em> L. and with drought tolerance in <em>Pinus massoniana</em> and <em>Pinus pinaster</em> Aiton. In red cedar (<em>Cedrela odorata</em> L.), the transcriptome was obtained by sequencing a single leaf, identifying 52,181 gene models. In the NCBI, EMBL-EBI, TreeGenes, PLAZA databases and the hardwood genomics website it is possible to find information related to the genomics and transcriptomics of timber species. <strong>Implications:</strong> More research is required in omics in timber, particularly in red cedar, since the search on these topics yielded little information. <strong>Conclusion</strong>: Through the bibliographic review in databases, the timber trees that have a described genome and transcriptome were identified. This information can be used for the assembly and annotation of new genomes, identification of genes and molecular markers, among other applications.</p>

Abstract 16746: Novel Role of Endothelial CD45 in Regulating Endothelial-to-Mesenchymal Transition (EndMT) in Atherosclerosis

Introduction: Atherosclerosis is the leading cause of mortality in the United States and most other developed countries. Endothelial cell (EC) activation is a hallmark of the initiation and progression of atherosclerosis; identification of molecular markers of dysfunctional endothelium represents a biological challenge to developing new therapeutic targets. CD45 is a marker of hematopoietic cells, which is rarely expressed in ECs. However, recent studies indicated that CD45 is indispensable in driving the endothelial-to-mesenchymal transition (EndMT) following myocardial infarction. EndMT has also been implicated in the pathogenesis of atheroma progression. Thus, we aim to investigate whether endothelial CD45 contributes to the progression of atherosclerosis by facilitating the EndMT. Methods and results: In vitro , we used CRISPR/inactive Cas9 transcriptional activation system to express CD45 in human endothelial colony-forming cells (ECFCs). Using FACS analyses, we found that CD45+ECFCs upregulate transforming growth factors (TGFβ 1-3 ) that implicate EndMT but downregulate FGFR1 expression, which exacerbates EndMT. qRT-PCR and WB showed that CD45+ECFCs downregulate transcription factors KLFs. In vivo , we generated a tamoxifen-inducible EC-specific CD45 deficient mouse strain (EC-CD45iKO) in ApoE-deficient (ApoE-/-) background and fed with a Western diet (C57BL/6) for atherosclerosis and molecular analyses. We found that ApoE-/- / EC-iCD45KO mice reduced plaque macrophages, foam cells, expression of adhesion molecule, and lesion development compared to ApoE-/- controls. Interestingly, ApoE-/- / EC-iCD45KO mice showed the reduction of α-smooth muscle actin, which is typical of EndMT, in the aortic plaque. Single-cell RNA-seq analyses have been performed to characterize that endothelial CD45 regulates the expression of pro-inflammatory, EndMT, and endothelial cell markers genes on the aortic ECs. Conclusion: These findings demonstrate that endothelial CD45 potentiates atherosclerosis by inducing TGF signaling and mesenchymal phenotype, causing FGFR1 downregulation and attenuating KLFs expression to drive EndMT, highlighting endothelial CD45 may be a new drug target for the treatment of atherosclerosis.

Multi-genome comprehensive identification of SSR/SV and development of molecular markers database to serve Sorghum bicolor (L.) breeding

BackgroundAs an important food and cash crop, identification of DNA molecular markers is of great significance for molecular marker-assisted breeding of Sorghum (Sorghum bicolor (L.) moench). Although some sorghum-related mutation databases have been published, the special SSR and SV databases still need to be constructed and updated.ResultsIn this study, the quality of 18 different sorghum genomes was evaluated, and two genomes were assembled at chromosome level. Through the identification and comparative analysis of SSR loci in these genomes, the distribution characteristics of SSR in the above sorghum genomes were initially revealed. At the same time, five representative reference genomes were selected to identify the structural variation of sorghum. Finally, a convenient SSR/SV database of sorghum was constructed by integrating the above results (http://www.sorghum.top:8079/;http://43.154.129.150:8079/;http://47.106.184.91:8079/). Users can query the information of related sites and primer pairs.ConclusionsAnyway, our research provides convenience for sorghum researchers and will play an active role in sorghum molecular marker-assisted breeding.

Variability for kernel starch components in Indian maize germplasm and identification of polymorphic molecular marker for selected waxy maize genotypes

Variability for kernel starch components in Indian maize germplasm and identification of polymorphic molecular marker for selected waxy maize genotypes

Advances in the research of exosomes in renal cell carcinoma: from mechanisms to applications.

Renal cell carcinoma (RCC) is one of the most malignant urological tumors. Currently, there is a lack of molecular markers for early diagnosis of RCC. The 5-year survival rate for early-stage RCC is generally favorable; however, the prognosis takes a significant downturn when the tumor progresses to distant metastasis. Therefore, the identification of molecular markers for RCC is crucial in enhancing early diagnosis rates. Exosomes are a type of extracellular vesicle (EV) typically ranging in size from 30 nm to 150 nm, which contain RNA, DNA, proteins, lipids, etc. They can impact neighboring receptor cells through the autocrine or paracrine pathway, influence cellular communication, and regulate the local immune cells, consequently shaping the tumor immune microenvironment and closely associating with tumor development. The clinical application of exosomes as tumor markers and therapeutic targets has ignited significant interest within the research community. This review aims to provide a comprehensive summary of the advancements in exosome research within the context of RCC.

Whole-genome surveillance identifies markers of Plasmodium falciparum drug resistance and novel genomic regions under selection in Mozambique.

Malaria is a devastating disease caused by Plasmodium parasites. The evolution of parasite drug resistance continues to hamper progress toward malaria elimination, and despite extensive efforts to control malaria, it remains a leading cause of death in Mozambique and other countries in the region. The development of successful vaccines and identification of molecular markers to track drug efficacy are essential for managing the disease burden. We present an analysis of the parasite genome in Mozambique, a country with one of the highest malaria burdens globally and limited available genomic data, revealing current selection pressure. We contribute additional evidence to limited prior studies supporting the effectiveness of SWGA in producing reliable genomic data from complex clinical samples. Our results provide the identity of genomic loci that may be associated with current antimalarial drug use, including artemisinin and lumefantrine, and reveal selection pressure predicted to compromise the efficacy of current vaccine candidates.

Characterization of a virulence factor in Plasmodiophora brassicae, with molecular markers for identification.

Symptom severity on differential host lines is currently used to characterize and identify pathotypes of Plasmodiophora brassicae, which is an obligate, soil-borne chromist pathogen that causes clubroot disease on canola (Brassica napus) and other brassica crops. This process is slow, variable and resource intensive; development of molecular markers could make identification of important pathotypes faster and more consistent for deployment of cultivars with pathotype-specific resistance. In the current study, a variant of gene 9171 was identified in the whole-genome sequences of only the highly virulent pathotypes of P. brassicae from around the world, including the new cohort of virulent pathotypes in Canada; its presence was confirmed using three KASP marker pairs. The gene was not present in the initial cohort of pathotypes identified in Canada. The putative structure, domains, and gene ontogeny of the protein product of gene 9171 were assessed using on-line software resources. Structural analysis of the putative protein produced by gene 9171 indicated that it was localized in the cytosol, and likely involved in cellular processes and catalytic activity. Identification of gene 9171 represents a potentially useful step toward molecular identification of the pathotypes of P. brassicae.

Identification of Molecular Markers Predicting the Outcome of Anti-thrombotic Therapy After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome and Atrial fibrillation: Evidence from a Meta-analysis and Experimental Study.

Acute coronary syndrome (ACS) and atrial fibrillation (AF) often coexist in clinical practice, and patients with these conditions often have a critical illness with high risk of both ischemia and bleeding. This study aims to report potential molecular markers for predicting the efficacy based on a meta-analysis of microarray data from the GEO database. In 40 patients with acute coronary syndrome (ACS) and atrial fibrillation (AF) treated with PCI, P2RX1's effects on platelet aggregation, medication resistance, and predictive value were examined. Twenty up-regulated genes in peripheral blood samples of ACS and AF patients were down-regulated after PCI, while 7 down-regulated genes were up-regulated. ACS affected eight potential genes. P2RX1, one of the four LASSO analysis-retrieved disease characteristic genes, accurately predicted AF patients' thrombosis risk and PCI's anti-thrombotic impact. Therefore, P2RX1 may be a molecular marker to predict the effect of anti-thrombotic therapy in patients with ACS and AF after PCI.

Identification of Characteristic lncRNA Molecular Markers in Osteoarthritis by Integrating GEO Database and Machine Learning Strategies and Experimental Validation

To screen for long non-coding RNA (lncRNA) molecular markers characteristic of osteoarthritis (OA) by utilizing the Gene Expression Omnibus (GEO) database combined with machine learning. The samples of 185 OA patients and 76 healthy individuals as normal controls were included in the study. GEO datasets were screened for differentially expressed lncRNAs. Three algorithms, the least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF), were used to screen for candidate lncRNA models and receiver operating characteristic (ROC) curves were plotted to evaluate the models. We collected the peripheral blood samples of 30 clinical OA patients and 15 health controls and measured the immunoinflammatory indicators. RT-PCR was performed for quantitative analysis of the expression of lncRNA molecular markers in peripheral blood mononuclear cells (PBMC). Pearson analysis was performed to examine the correlation between lncRNA and indicators for inflammation of the immune system. A total of 14 key markers were identified with LASSO, 6 genes were identified with SVM-RFE, and 24 genes were identified with RF. Venn diagram was used to screen for overlapping genes identified with the three algorithms, showing HOTAIR, H19, MIR155 HG, and NKILA to be the overlapping genes. The ROC curves showed that these four lncRNAs all had an area under the curve ( AUC) greater than 0.7. The RT-PCR findings revealed relatively elevated expression of HOTAIR, H19, and MIR155HG and decreased expression of NKILA in the PBMC of OA patients compared with those of the normal group ( P<0.01). The results were consistent with the bioinformatics predictions. Pearson analysis showed that the candidate lncRNAs were correlated with clinical indicators for inflammation. HOTAIR, H19, MIR155 HG, and NKILA can be used as molecular markers for the clinical diagnosis of OA and are correlate with clinical indicators of inflammation of the immune system.

Development and validation of a differentiation-related signature based on single-cell RNA sequencing data of immune cells in spinal cord injury

BackgroundAfter spinal cord injury (SCI), the native immune surveillance function of the central nervous system is activated, resulting in a substantial infiltration of immune cells into the affected tissue. While numerous studies have explored the transcriptome data following SCI and revealed certain diagnostic biomarkers, there remains a paucity of research pertaining the identification of immune subtypes and molecular markers related to the immune system post-spinal cord injury using single-cell sequencing data of immune cells. MethodsThe researchers conducted an analysis of spinal cord samples obtained at three time points (3,10, and 21 days) following SCI using the GSE159638 dataset. The SCI subsets were delineated through pseudo-time analysis, and differentiation related genes were identified after principal component analysis (PCA), cell clustering, and annotation techniques. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed to assess the differentiation-related genes (DRGs) across different subsets. The molecular subtypes of SCI were determined using consensus clustering analysis. To further explore and validate the correlation between the molecular subtypes and the immune microenvironment, the CIBERSORT algorithm was employed. High-value diagnostic gene markers were identified using LASSO regression, and their diagnostic sensitivity was assessed using receiver operating characteristic curves (ROC) and quantitative real-time polymerase chain reaction (qRT-PCR). ResultsThree SCI subsets were obtained, and differentiation-related genes were characterized. Within these subsets, two distinct molecular subtypes, namely C1 and C2, were identified. These subtypes demonstrated significant variations in terms of immune cell infiltration levels and the expression of immune checkpoint genes. Through further analysis, three candidate biomarkers (C1qa, Lgals3 and Cd63) were identified and subsequently validated. ConclusionsOur study revealed a diverse immune microenvironment in SCI samples, highlighting the potential significance of C1qa, Lgals3 and Cd63 as immune biomarkers for diagnosing SCI. Moreover, the identification of immune checkpoints corresponding to the two molecular subtypes suggests their potential as targets for immunotherapy to enhance SCI repair in future interventions.

Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies.

Cellular senescence is a response to a wide variety of stressors, including DNA damage, oncogene activation and physiologic aging, and pathologically accelerated senescence contributes to human disease, including diabetes mellitus. Indeed, recent work in this field has demonstrated a role for pancreatic β-cell senescence in the pathogenesis of Type 1 Diabetes, Type 2 Diabetes and monogenic diabetes. Small molecule or genetic targeting of senescent β-cells has shown promise as a novel therapeutic approach for preventing and treating diabetes. Despite these advances, major questions remain around the molecular mechanisms driving senescence in the β-cell, identification of molecular markers that distinguish senescent from non-senescent β-cell subpopulations, and translation of proof-of-concept therapies into novel treatments for diabetes in humans. Here, we summarize the current state of the field of β-cell senescence, highlighting insights from mouse models as well as studies on human islets and β-cells. We identify markers that have been used to detect β-cell senescence to unify future research efforts in this field. We discuss emerging concepts of the natural history of senescence in β-cells, heterogeneity of senescent β-cells subpopulations, role of sex differences in senescent responses, and the consequences of senescence on integrated islet function and microenvironment. As a young and developing field, there remain many open research questions which need to be addressed to move senescence-targeted approaches towards clinical investigation.

Identification and interest of molecular markers to monitor plant Pi status

BackgroundInorganic phosphate (Pi) is the sole source of phosphorus for plants. It is a limiting factor for plant yield in most soils worldwide. Due to economic and environmental constraints, the use of Pi fertilizer is and will be more and more limited. Unfortunately, evaluation of Pi bioavailability or Pi starvation traits remains a tedious task, which often does not inform us about the real Pi plant status.ResultsHere, we identified by transcriptomic studies carried out in the plant model Arabidopsis thaliana, early roots- or leaves-conserved molecular markers for Pi starvation, exhibiting fast response to modifications of phosphate nutritional status. We identified their homologues in three crops (wheat, rapeseed, and maize) and demonstrated that they offer a reliable opportunity to monitor the actual plant internal Pi status. They turn out to be very sensitive in the concentration range of 0-50 µM which is the most common case in the vast majority of soils and situations where Pi hardly accumulates in plants. Besides in vitro conditions, they could also be validated for plants growing in the greenhouse or in open field conditions.ConclusionThese markers provide valuable physiological tools for plant physiologists and breeders to assess phosphate bio-availability impact on plant growth in their studies. This also offers the opportunity to cope with the rising economical (shortage) and societal problems (pollution) resulting from the management of this critical natural resource.

Haplotype analysis of QTLs governing early seedling vigor-related traits under dry-direct-seeded rice (Oryza sativa L.) conditions.

The eventual shifting of cultivation method from puddle transplanted rice to direct-seeded rice (DSR) to save water prompted researchers to develop DSR-suitable varieties. To achieve this, identification of molecular markers associated with must-have traits for DSR, especially early seedling vigour related traits is crucial. In the present investigation, the haplotype analysis using flanking markers of three important quantitative trait loci (QTLs) for early seedling vigour-related traits viz., qSV-6a (RM204 and RM402) for root length; qVI (RM20429 and RM3) for seedling vigour index; qGP-6 (RM528 and RM400) for germination percentage revealed that the marker alleles were found to show significant associations with qVI and qGP-6 QTLs. The majority of genotypes with high early seedling vigour are with qVIHap-1 (220 and 160 bp) and qGPHap-1 (290 and 290 bp). The rice genotypes with superior haplotypes for early seedling vigour are BMF536, BMF540, BMF525, MM129 and MDP2. In conclusion, here we demonstrated that the markers RM20429 and RM3 are associated with seedling vigour index whereas RM528 and RM400 are associated with germination percentage. Therefore, these markers can be utilized to develop varieties suitable for DSR conditions through haplotype-based breeding. In addition, the rice genotypes with superior haplotypes can be of immense value to use as donors or can be released as varieties also under DSR conditions.

The screening and validation process of miR-223-3p for saliva identification

More accurate identification of the types of body fluids left at a crime scene is indispensable for improving the judicial chain of evidence. MicroRNAs (miRNAs) have become recognized as ideal molecular markers for the identification of body fluids in forensic science due to their short length, stability and high tissue specificity. In this study, small RNA sequencing was performed on 20 samples of five types of body fluids (peripheral blood, menstrual blood, saliva, semen, and vaginal secretions) with the BGISEQ-500 sequencing platform, and the specific miRNA markers of saliva and vaginal secretions were screened by bioinformatics methods, including differential expression analysis and significant enrichment analysis. Through RT-qPCR validation of 169 samples, we confirmed that miR-223-3p can be used as a saliva-specific marker. In addition, we considered miR-223-3p in combination with four other miRNA molecules (miR-451a, miR-891a-5p, miR-144-5p, miR-203a-3p) that had been previously screened and verified in our laboratory, and seven body fluid prediction models based on machine learning algorithms were constructed and verified. The results showed that a kernel density estimation (KDE) model based on the five miRNA markers for body fluid identification could achieve 100% accuracy in the samples tested in the present study.

PARP10 is highly expressed and associated with inferior outcomes in acute myeloid leukemia.

Acute myeloid leukemia is a heterogeneous disease of the hematopoietic system, which possesses a poor prognosis; thus, the identification of novel molecular markers is urgently needed to better define the risk stratification and optimize treatment therapies for this disease. Here, we investigated the roles of the PARP family genes in AML by analyzing their mRNA expression profiles and their association with clinical features using data from TCGA and GSE. Our results showed that PARP10 was significantly more highly expressed in AML samples than in normal controls, and high expression of PARP10 was associated with older age (≥60 years, P = 0.012), more frequent TP53 mutations (P = 0.024), high-risk stratification (P < 0.05), and poorer outcomes (P < 0.05). Patients with high expression of PARP10 exhibited significantly poorer overall survival (OS) and event-free survival (EFS) than those with low PARP10 expressions (OS: median: 0.88 vs. 2.19 years; P = 0.001; EFS: median: 0.65 vs. 1.12 years; P = 0.041). Multivariate analysis indicated that high expression of PARP10 was an independent risk factor for poorer OS and EFS in AML patients. Moreover, we found that allo-SCT improved OS for AML patients with high PARP10 expression but not for patients with low PARP10 expression, while allo-SCT decreased EFS for patients with low PARP10 expression. Finally, we confirmed that PARP10 knockout impaired AML cell proliferation in vitro. In summary, our data suggested that PARP10 is aberrantly expressed in AML, and high expression of PARP10 might be a biomarker for poor prognosis and also a potential indicator for allo-SCT therapy, which might provide precise treatment indications for physicians.