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PubMed2026

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals↗

PubMed2004

Smc01944, a secreted peroxidase induced by oxidative stresses in Sinorhizobium meliloti 1021.

Sequencing of the Sinorhizobium meliloti strain 1021 genome led to the detection of 6204 open reading frames, 41 % of which have no hypothetical function. To help annotate this genome, a transcriptome analysis was carried out with a dedicated microarray consisting of 146 genes belonging to three different classes: (i) no hypothetical function; (ii) potentially involved in oxidative stress responses; (iii) known to participate in oxidative stress responses (e.g. catalase and superoxide dismutase genes). This transcriptome analysis, together with biological experiments and in silico investigations, identified new genes induced by exogenous H(2)O(2). The smc01944 gene was the most strongly induced: quantitative PCR showed that the amount of smc01944 mRNA increased 50-fold following the addition of 10 mM H(2)O(2), whereas the amount of katA mRNA (encoding a catalase) only increased 10-fold. Smc01944 is a non-haem chloroperoxidase (Cpo). The only member of this family to have been so far characterized is encoded by prxC of Pseudomonas fluorescens. Unexpectedly, the NH(2)-terminus of Smc01944 includes a signal peptide and Smc01944 is secreted into the supernatant. Interestingly, smc01944 is preceded by smc01945, encoding an OhrR-like regulator (MarR family). Thus, Smc01944 is the first exported Cpo encoded by a gene possibly regulated by an OhrR regulator. It was also shown that smc01944 is induced by t-butyl and cumene hydroperoxides but only slightly by menadione. The study of Smc01944 described in this work showed that the oxidative stress response of S. meliloti seems to differ from that of other bacteria characterized to date.

Amino Acid Sequence↗

PubMed2026

Transcriptomic Changes Associated with Electroacupuncture in a DMCAO Model of Delayed Cognitive Impairment.

INTRODUCTION: Delayed Cognitive Impairment (DCIS) occurs in approximately 31% to 77% of individuals following stroke. Clinical findings have indicated that electroacupuncture may alleviate post-stroke DCIS. However, insights derived from animal models remain limited. The present study utilized a Distal Middle Cerebral Artery Occlusion (DMCAO) mouse model to investigate the potential mechanisms of electroacupuncture through hippocampal transcriptomic analysis. MATERIALS AND METHODS: Adult male BALB/c mice were subjected to DMCAO and received electroacupuncture treatment. High-throughput RNA sequencing of hippocampal tissue was performed to identify Differentially Expressed Genes (DEGs). Enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, hierarchical clustering, and Protein-Protein Interaction (PPI) network analysis, were performed to elucidate potential biological mechanisms. RESULTS: The DMCAO model exhibited features consistent with DCIS. Electroacupuncture treatment was associated with improved cognitive performance and enhanced hippocampal neuroplasticity. A total of 116 DEGs were identified in the DMCAO group compared with the sham group, while 69 DEGs were identified in the DMCAO + electroacupuncture group compared with the untreated DMCAO group. DISCUSSION: GO enrichment analysis indicated that electroacupuncture modulated biological processes related to nerve fibers, axonal development, neuronal regulation, cellular processes, and cardiovascular protection. KEGG pathway analysis indicated involvement in pathways associated with neuronal recovery and axonal function. The PPI network comprised 28 nodes and 33 interactions, with hub genes such as Gna13, Hipk2, and Stambp playing key roles. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) results were consistent with RNA sequencing findings. CONCLUSION: Electroacupuncture improved DCIS in the DMCAO mouse model. Transcriptomic analysis of the hippocampus provided preliminary evidence of the potential mechanisms underlying the therapeutic effects of electroacupuncture treatment following ischemic stroke.

Animals↗

PubMed2004

Directed evolution of pyruvate decarboxylase-negative Saccharomyces cerevisiae, yielding a C2-independent, glucose-tolerant, and pyruvate-hyperproducing yeast.

The absence of alcoholic fermentation makes pyruvate decarboxylase-negative (Pdc(-)) strains of Saccharomyces cerevisiae an interesting platform for further metabolic engineering of central metabolism. However, Pdc(-) S. cerevisiae strains have two growth defects: (i) growth on synthetic medium in glucose-limited chemostat cultures requires the addition of small amounts of ethanol or acetate and (ii) even in the presence of a C(2) compound, these strains cannot grow in batch cultures on synthetic medium with glucose. We used two subsequent phenotypic selection strategies to obtain a Pdc(-) strain without these growth defects. An acetate-independent Pdc(-) mutant was obtained via (otherwise) glucose-limited chemostat cultivation by progressively lowering the acetate content in the feed. Transcriptome analysis did not reveal the mechanisms behind the C(2) independence. Further selection for glucose tolerance in shake flasks resulted in a Pdc(-) S. cerevisiae mutant (TAM) that could grow in batch cultures ( micro (max) = 0.20 h(-1)) on synthetic medium, with glucose as the sole carbon source. Although the exact molecular mechanisms underlying the glucose-tolerant phenotype were not resolved, transcriptome analysis of the TAM strain revealed increased transcript levels of many glucose-repressible genes relative to the isogenic wild type in nitrogen-limited chemostat cultures with excess glucose. In pH-controlled aerobic batch cultures, the TAM strain produced large amounts of pyruvate. By repeated glucose feeding, a pyruvate concentration of 135 g liter(-1) was obtained, with a specific pyruvate production rate of 6 to 7 mmol g of biomass(-1) h(-1) during the exponential-growth phase and an overall yield of 0.54 g of pyruvate g of glucose(-1).

Culture Media↗

PubMed2005

Combined global localization analysis and transcriptome data identify genes that are directly coregulated by Adr1 and Cat8.

In Saccharomyces cerevisiae, glucose depletion causes a profound alteration in metabolism, mediated in part by global transcriptional changes. Many of the transcription factors that regulate these changes act combinatorially. We have analyzed combinatorial regulation by Adr1 and Cat8, two transcription factors that act during glucose depletion, by combining genome-wide expression and genome-wide binding data. We identified 32 genes that are directly activated by Adr1, 28 genes that are directly activated by Cat8, and 14 genes that are directly regulated by both. Our analysis also uncovered promoters that Adr1 binds but does not regulate and promoters that are indirectly regulated by Cat8, stressing the advantage of combining global expression and global localization analysis to find directly regulated targets. At most of the coregulated promoters, the in vivo binding of one factor is independent of the other, but Adr1 is required for optimal Cat8 binding at two promoters with a poor match to the Cat8 binding consensus. In addition, Cat8 is required for Adr1 binding at promoters where Adr1 is not required for transcription. These data provide a comprehensive analysis of the direct, indirect, and combinatorial requirements for these two global transcription factors.

Chromatin Immunoprecipitation↗

PubMed2004

Expression of cardiac myosin-binding protein-C (cMyBP-C) in Drosophila as a model for the study of human cardiomyopathies.

Mutations in the MYBPC3 gene encoding human cardiac myosin-binding protein-C (cMyBP-C) are associated with familial hypertrophic cardiomyopathy (FHC), but the molecular mechanisms involved are not fully understood. In addition, development of FHC is sensitive to genetic background, and the search for candidate modifier genes is crucial with a view to proposing diagnosis and exploring new therapies. We used Drosophila as the model to investigate the in vivo consequences of human cMyBP-C mutations. We first produced transgenic flies that specifically express human wild-type or two C-terminal truncated cMyBP-Cs in indirect flight muscles (IFM), a tissue particularly amenable to genetic and molecular analyses. First, incorporation of human cMyBP-C into the IFM led to sarcomeric structural abnormalities and to a flightless phenotype aggravated by age and human gene dosage. Second, transcriptome analysis of transgenic IFM using nylon microarrays showed the remodelling of a transcriptional program involving 97 out of 3570 Drosophila genes. Among them, the Calmodulin gene encoding a key component of muscle contraction, found up-regulated in transgenic IFM, was evaluated as a potential modifier gene. Calmodulin mutant alleles rescued the flightless phenotype, and therefore behave as dominant suppressors of the flightless phenotype suggesting that Calmodulin might be a modifier gene in the context of human FHC. In conclusion, we suggest that the combination of heterologous transgenesis and transcriptome analysis in Drosophila could be of great value as a way to glean insights into the molecular mechanisms underlying FHC and to propose potential candidate modifier genes.

Animals↗

PubMed2026

Transcriptomic Insights into Acupuncture Mechanisms in Protecting Ovarian Function in Mice with Premature Ovarian Insufficiency.

OBJECTIVE: To explore the molecular mechanisms underlying the protective effect of acupuncture on ovarian function in mice with cyclophosphamide-induced premature ovarian insufficiency (POI) via transcriptomic analysis. METHODS: Twenty female C57BL/6 mice were divided into 4 groups: control, model, acupuncture, and non-meridian/non-acupoint (NOMA). POI was induced in the model, acupuncture, and non-meridian/non-acupoint groups via cyclophosphamide injection. The acupuncture group received acupuncture at Guanyuan (CV 4), bilateral Guilai (ST 29), and Sanyinjiao (SP 6) for 3 weeks. After the intervention, ovarian tissue weight and ovarian coefficient were calculated, serum levels of key reproductive hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were detected, and ovarian histopathological changes were observed to evaluate ovarian function. Transcriptome sequencing was performed to identify differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore key functional terms and signaling pathways. Western blot was finally applied to validate the expression of core proteins related to mitochondrial function, endoplasmic reticulum stress and inflammatory pathways. RESULTS: The model group showed reduced ovarian weight and elevated FSH levels. The acupuncture group exhibited significantly higher ovarian weight and coefficient, lower FSH levels, and increased E2 and AMH levels compared to the model group (all P<0.01). Transcriptomic analysis revealed 4,021 DEGs between groups. GO and KEGG analyses revealed that these DEGs were mainly involved in oocyte development, steroid hormone synthesis, and pathways related to mitochondrial function, endoplasmic reticulum stress, and inflammatory signaling. Western blot analysis showed that acupuncture partially restored mitochondrial function markers cytochrome c oxidase subunit IV and NADH dehydrogenase 1 beta subcomplex subunit 8 and reduced endoplasmic reticulum stress markers (glucose-regulated protein 78 and Calnexin, P<0.01). It also downregulated pro-inflammatory proteins (IL-17R, IL-17A, NF-κB p65, p-NF-κB p65, ERK1/2, and p-ERK1/2) and upregulated proteins related to metabolic homeostasis (peroxisome proliferator-activated receptor γ, receptor-interacting protein 140, nicotinamide phosphoribosyltransferase, and sirtuin 1, P<0.01). CONCLUSION: Acupuncture effectively alleviates cyclophosphamide-induced POI in mice, improves ovarian function and follicular quality by regulating cellular functions and inflammatory pathways, suggesting a novel therapeutic approach for POI.

acupuncture↗

PubMed2002

Analysis of transcriptomes of human malaria parasite Plasmodium falciparum using full-length enriched library: identification of novel genes and diverse transcription start sites of messenger RNAs.

Now that the sequencing of the complete genome of the human malaria parasite Plasmodium falciparum is now underway, importance of analyses of complementary DNAs (cDNAs) is looming up. We constructed a full-length-enriched cDNA library from erythrocytic stage P. falciparum using the 'oligo-capping' method (Nucleic Acids Res. 29 (2001) 70). In this report we describe the novel genes identified using this library and detailed characterization of transcriptional start site of knob-associated histidine rich protein gene. Contrary to the previous report we conclude all the transcripts of plasmodium genes have diverse start sites. Sequence comparisons between the cDNAs and the complete sequences of chromosomes 2 identified three novel genes that had been missed by computational predictions. Moreover, analysis of transcriptional start sites revealed that the average length of the 5' untranslated region was 346 nt, which is much longer than that in humans. The transcriptional start sites of all the genes studied were far more diverse than those of human genes. These observations may reflect unique mechanism(s) of gene expression in this organism, which has an extremely AT-rich genome.

5' Untranslated Regions↗

PubMed2005

Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia.

Understanding the complexity and dynamics of cancer cells in response to effective therapy requires hypothesis-driven, quantitative, and high-throughput measurement of genes and proteins at both spatial and temporal levels. This study was designed to gain insights into molecular networks underlying the clinical synergy between retinoic acid (RA) and arsenic trioxide (ATO) in acute promyelocytic leukemia (APL), which results in a high-quality disease-free survival in most patients after consolidation with conventional chemotherapy. We have applied an approach integrating cDNA microarray, 2D gel electrophoresis with MS, and methods of computational biology to study the effects on APL cell line NB4 treated with RA, ATO, and the combination of the two agents and collected in a time series. Numerous features were revealed that indicated the coordinated regulation of molecular networks from various aspects of granulocytic differentiation and apoptosis at the transcriptome and proteome levels. These features include an array of transcription factors and cofactors, activation of calcium signaling, stimulation of the IFN pathway, activation of the proteasome system, degradation of the PML-RARalpha oncoprotein, restoration of the nuclear body, cell-cycle arrest, and gain of apoptotic potential. Hence, this investigation has provided not only a detailed understanding of the combined therapeutic effects of RA/ATO in APL but also a road map to approach hematopoietic malignancies at the systems level.

Antineoplastic Agents↗

PubMed2004

Comparative gene-based in silico analysis of transcriptomes in different bovine tissues and (or) organs.

A gene-based approach was used to annotate 322,168 cattle expressed sequence tags (ESTs) based on human genes in order to census the transcriptomes, analyze their expression similarities, and identify genes preferentially expressed in different bovine tissues and (or) organs. Of the 34,157 human coding genes used in a standalone BLAST search, 14,928 could be matched with provisional orthologous sequences in a total of 230,135 bovine ESTs. The remaining 92,033 bovine ESTs were estimated to represent an additional 5970 genes in cattle. On average, approximately 8600 genes were estimated to be expressed in a single tissue and (or) organ and 13,000 in a pooled tissue library. On the basis of the estimated numbers of genes, no more than 3% of genes would be missed when approximately 34,000 ESTs were sequenced from a single tissue and (or) organ library and approximately 40,000 ESTs from a pooled source, respectively. Cluster analyses of the gene expression patterns among 12 single tissues and (or) organs in cattle revealed that their expression similarities would depend on physiological functions. In addition, a total of 1502 genes were identified as preferentially expressed genes in these 12 single tissues and (or) organs with LOD (logarithm of the odds, base 10) > or = 3.0. Therefore, our study provides some insights for further investigating the developmental and functional relations of various tissues and organs in mammals.

Animals↗

PubMed2026

Thyroid hormone deprivation creates an immunological signature in the mouse liver, involving Kupffer cell presentation as the mouse ages.

PURPOSE: Aging is associated with an increased prevalence of chronic liver diseases suggesting impaired immune and metabolic function. In addition, thyroid hormone (TH) impacts liver physiology and TH deprivation or excess negatively affect organ maintenance. However, whether age-dependent consequences of TH alterations are reflected in a liver-specific adaptation is unknown so far. The present study aimed to characterize the impact of TH deprivation or excess on the liver transcriptome during aging. METHODS: Five- and 21-month-old male C57BL/6 mice were exposed either to chronic TH deprivation or to chronic TH excess and compared to control treatment by microarray-based liver transcriptome analysis. RESULTS: Significant roles of both TH state and age became obvious: Bioinformatic analysis of the liver transcriptome data revealed an age-dependent immune signature by chronic TH deprivation, an age-dependent immune and metabolic signature independent of exogenous TH modulation, as well as an age-dependent metabolic signature by chronic TH excess. Published data of single cell transcriptomic atlas characterizing aging tissues in the mouse were compared with our data and revealed Kupffer cell presentation in the immunological signature by TH deprivation during aging. Literature data for four prominent differentially expressed genes, namely C1qb, C3ar1, Ctss, and Msr1, revealed that the complement system, extracellular matrix remodelling, as well as the proinflammatory phenotype of Kupffer cells are altered by TH deprivation during aging. CONCLUSION: In conclusion, our study illuminates the interplay between TH deprivation, aging, and liver transcriptome signatures, highlighting potential implications for immune function and tissue maintenance, particularly through the modulation of Kupffer cell presentation.

Animals↗

PubMed2005

Correlation of codon bias measures with mRNA levels: analysis of transcriptome data from Escherichia coli.

Although codon usage is often represented by a 61-dimensional vector, the ability of determining the codon bias in a gene relies on a uni-dimensional vector which measures the total bias in usage of synonymous codons. Codon usage is receiving more and more focus because codon biases might be valuable tools to predict and optimize gene/protein expression. How good any of these measures is for correlating codon usage with gene and protein expression has yet to be investigated. In this study, we correlated gene transcript levels in Escherichia coli with codon usage, using a number of different codon bias measures. We found that there is a significant correlation between transcript levels and codon bias measures, suggesting that these measures can be used to assess or predict gene expression. The codon bias measure performing best in this context was the codon adaptation index.

Codon↗

PubMed2005

Adaptation of Corynebacterium glutamicum to ammonium limitation: a global analysis using transcriptome and proteome techniques.

Theresponse of Corynebacterium glutamicum to ammonium limitation was studied by transcriptional and proteome profiling of cells grown in a chemostat. Our results show that ammonium-limited growth of C. glutamicum results in a rearrangement of the cellular transport capacity, changes in metabolic pathways for nitrogen assimilation, amino acid biosynthesis, and carbon metabolism, as well as a decreased cell division. Since transcription at different growth rates was studied, it was possible to distinguish specific responses to ammonium limitation and more general, growth rate-dependent alterations in gene expression. The latter include a number of genes encoding ribosomal proteins and genes for F(o)F(1)-ATP synthase subunits.

Adaptation, Physiological↗

PubMed2002

Renal transcriptomes: segmental analysis of differential expression.

BACKGROUND/AIMS: Progress accomplished by complete genomes and cDNA-sequencing projects calls for methods that fully use these resources to study gene expression patterns in characterized cell populations. However, since the number of functional genes cannot be readily inferred from the genomic sequence, it is highly desirable to make use of methods enabling to study both known and unknown genes. METHODS: The method of serial analysis of gene expression provides short diagnostic cDNA tags without bias towards known genes. In addition, the frequency of each tag in the library conveys quantitative information on gene expression. A microassay was set-up to perform serial analysis of gene expression in minute samples such as those obtained by microdissecting nephron segments. RESULTS: Studies carried out in the thick ascending limb of Henle's loop and the collecting duct of the mouse kidney provided expression data for several thousand genes. Known markers were found appropriately enriched, and several of the thick ascending limb or collecting duct specific transcripts had no database match. CONCLUSIONS: The microassay for serial analysis of gene expression makes possible large-scale quantitative measurements of mRNA levels in nephron segments. The comprehensive picture generated by analyzing both known and unknown transcripts in defined cell populations should help to discover genes with dedicated functions.

Animals↗

PubMed2002

Impact of genomics approaches on plant genetics and physiology.

Comprehensive analysis of genetic information in higher plants is under way for several plants of biological and agronomical importance. Among them, Arabidopsis thaliana, a member of Brassica family, and Oryza sativa(rice) have been chosen as model plants most suitable for genome analysis. Sequencing of the genome of A. thaliana was completed in December 2000, and rice genome sequencing is in progress. The accumulated genome sequences, together with the hundreds of thousands of ESTs from several tens of plant species, have drastically changed the strategy of plant genetics. By utilizing the information on the genome and gene structures, comprehensive approaches for genome-wide functional analysis of the genes, including transcriptome analysis using microarray systems and a comprehensive analysis of a large number of insertion mutant lines, have been widely adopted. As a consequence, a large quantity of information on both the structure and function of genes in these model plants has been accumulated. However, other plant species may have their own characteristics and advantages to study individual phenomena. Application of knowledge from the model plants to other plant species and vice versa through the common language, namely the genome information, should facilitate understanding of the genetic systems underlying a variety of biological phenomena. Introduction of this common language may not be very simple, especially in the case of complex pathways such as a process of cell-covering formation. Nevertheless, it should be emphasized that genomics approaches are the most promising way to understand these processes.

Journal Article↗

PubMed2002

[Transcriptomes for serial analysis of gene expression].

The availability of the sequences for whole genomes is changing our understanding of cell biology. Functional genomics refers to the comprehensive analysis, at the protein level (proteome) and at the mRNA level (transcriptome) of all events associated with the expression of whole sets of genes. New methods have been developed for transcriptome analysis. Serial Analysis of Gene Expression (SAGE) is based on the massive sequential analysis of short cDNA sequence tags. Each tag is derived from a defined position within a transcript. Its size (14 bp) is sufficient to identify the corresponding gene and the number of times each tag is observed provides an accurate measurement of its expression level. Since tag populations can be widely amplified without altering their relative proportions, SAGE may be performed with minute amounts of biological extract. Dealing with the mass of data generated by SAGE necessitates computer analysis. A software is required to automatically detect and count tags from sequence files. Criterias allowing to assess the quality of experimental data can be included at this stage. To identify the corresponding genes, a database is created registering all virtual tags susceptible to be observed, based on the present status of the genome knowledge. By using currently available database functions, it is easy to match experimental and virtual tags, thus generating a new database registering identified tags, together with their expression levels. As an open system, SAGE is able to reveal new, yet unknown, transcripts. Their identification will become increasingly easier with the progress of genome annotation. However, their direct characterization can be attempted, since tag information may be sufficient to design primers allowing to extend unknown sequences. A major advantage of SAGE is that, by measuring expression levels without reference to an arbitrary standard, data are definitively acquired and cumulative. All publicly available data can thus be stored in a unique database, facilitating whole-genome analysis of differential expression between cell types, normal and diseased samples, or samples with and without drug treatment. SAGE data are readily amenable to statistical comparisons, allowing to determine the level of confidence of the observed variations. A major limitation of SAGE is that, because each analysis is obligatory performed on the whole set of expressed genes, it can hardly be performed on multiple samples, for example in kinetics studies or to compare the effects of large numbers of drugs. To overcome this limitation, high-throughput detection of a subset of mRNAs is more rapidly performed by parallel hybridization of mRNAs on arrays of nucleic acids immobilized on solid supports. From this point of view, a SAGE platform is a powerful instrument for selecting the most informative subset of genes, assembling them to design microarrays dedicated to a specific problem and calibrating measurement by comparison with a standard cell model for which SAGE data are available. This approach is an attractive alternative to strategies based exclusively on pangenomic arrays. A very large amount of SAGE data are already available and the problem is now to extract their biological meaning. Knowledge on metabolic pathways is already organized so that its successful integration in a SAGE platform can be undertaken. For other cell components and pathways, the problem lies on the lack of controlled vocabulary to describe gene activities, starting form a clear definition of the concept of biological function itself. Progress in gene and cell ontology is expected to facilitate computer-based extraction of biological knowledge from existing and forthcoming SAGE data.

Animals↗

PubMed2026

Comprehensive analysis of metabolomics and transcriptomics of radiation-induced rectal injury.

Radiation-induced rectal injury (RRI) significantly affects the quality of life in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NCRT). Non-targeted liquid chromatography-mass spectrometry metabolomics analysis and transcriptomic analysis were conducted to explore RRI characteristics. Hematoxylin-eosin and Masson staining confirmed radiation-induced injury in rectal tissue within the radiotherapy target region. Orthogonal partial least squares discriminant analysis identified 823 differentially expressed metabolites (DEMs). Transcriptomic analysis revealed 400 differentially expressed genes (DEGs). Enrichment analysis revealed that DEMs and DEGs were primarily involved in metabolic, immune, and signal transduction pathways. Integrated analysis demonstrated significant enrichment of DEMs and DEGs in the arachidonic acid metabolism pathway. Pearson's correlation and canonical correlation analyses were used to assess the association between DEMs and DEGs within this pathway. In conclusion, this study identified key biological regulatory pathways involved in RRI through a multi-omics approach, offering potential targets for its diagnosis and treatment.

Humans↗

PubMed2025

Whole blood transcriptome profile identifies motor neurone disease RNA biomarker signatures.

Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression profiles in (motor neurone disease) MND patients to the control subjects. We compared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND. In addition to the formal differential analysis, we performed functional annotation of the genomics data and identified the molecular pathways that are differentially regulated in MND patients. We identified 12,972 genes differentially expressed in the blood of MND patients compared to age and sex-matched controls. Functional genomic annotation identified activation of the pathways related to neurodegeneration, RNA transcription, RNA splicing and extracellular matrix reorganisation. Blood-based whole transcriptomic analysis can reliably differentiate MND patients from controls and can provide useful information for the clinical management of the disease and clinical trials.

Humans↗