SEARCH · PubMed Health

Results for “comparative transcriptomics”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources

PubMed2004

Anomalies in the expression profile of interspecific hybrids of Drosophila melanogaster and Drosophila simulans.

When females of Drosophila melanogaster and males of Drosophila simulans are mated, the male progeny are inviable, whereas the female progeny display manifold malformations and are sterile. These abnormalities result from genetic incompatibilities accumulated since the time the lineages of the species diverged, and may have their origin in aberrant gene transcription. Because compensatory changes within species may obscure differences at the regulatory level in conventional comparisons of the expression profile between species, we have compared the gene-expression profile of hybrid females with those of females of the parental species in order to identify regulatory incompatibilities. In the hybrid females, we find abnormal levels of messenger RNA for a large fraction of the Drosophila transcriptome. These include a gross underexpression of genes preferentially expressed in females, accompanying gonadal atrophy. The hybrid females also show significant overexpression of male-biased genes, which we attribute to incompatibilities in the regulatory mechanisms that normally act to control the expression of these genes in females. The net result of the multiple incompatibilities is that the gene-expression profiles of the parental females are more similar to each other than either is to that of the hybrid.

Animals↗

PubMed2026

Targeting super-enhancer-driven SKIL transcription by CDK7 inhibitor THZ1 to suppress gastric cancer progression.

BACKGROUND: Gastric cancer (GC) is a lethal malignancy characterized by high incidence, mortality, and limited treatment options. Transcriptional addiction is a key cancer hallmark that drives tumor pathogenesis, making its inhibition a promising therapeutic strategy for GC. The study aims to investigate the roles and mechanisms of super-enhancer (SE)-driven oncogenic transcriptional addiction in GC progression and to identify novel targetable vulnerabilities. METHODS: We utilized cellular and animal models to assess the effects of THZ1 treatment and CDK7 knockdown on GC progression. RNA sequencing was employed to elucidate the potential molecular mechanism of THZ1 treatment. ChIP-seq was performed to establish SE landscape in GC. Integrative analysis of transcriptomic and SE profiling was used to identify THZ1-targeted oncogenic genes. Rescue experiments were conducted to confirm that THZ1 treatment suppresses GC malignant progression by targeting SE-driven SKIL transcription. RESULTS: GC cells exhibited pronounced sensitivity to THZ1 compared to normal gastric mucosa cells, and the treatment potently suppressed tumor growth and migration in both cellular and animal models. CDK7 was significantly upregulated in GC tissues, and its knockdown inhibited malignant progression in vitro and in vivo, whereas its overexpression accelerated tumor progression. Mechanistically, SE-driven oncogenic transcriptional amplification underlies GC cell susceptibility to THZ1, supported by the identification of novel oncogenic genes such as SKIL. SKIL, a key Hippo pathway regulator, was highly expressed in GC cells, and its elevated expression predicted poor patient prognosis. SKIL silencing attenuated malignant phenotypes, while its overexpression diminished THZ1’s suppression of GC cell proliferation and migration. CONCLUSION: Our findings demonstrate that THZ1 inhibits GC progression by disrupting SE-driven oncogenic transcription, thereby offering CDK7 inhibition as a promising therapeutic intervention for GC.

Stomach Neoplasms↗

PubMed2026

Decoding age-stratified clinical and molecular heterogeneity in male breast cancer through multiomic profiling.

OBJECTIVE: Age-associated molecular heterogeneity is well described in female breast cancer but remains insufficiently characterized in male breast cancer (MBC). We profiled age-stratified clinical and molecular differences between younger (≤55 years) male breast cancer (YMBC) and older (>55 years) male breast cancer (OMBC). METHODS: We retrospectively analyzed 347 patients with MBC diagnosed at Fudan University Shanghai Cancer Center by integrating clinicopathological data, RNA sequencing, and whole-exome sequencing (WES). Survival, differential expression, and mutational signature analyses were performed. Tumor microenvironment features were inferred using xCell and ESTIMATE, and weighted gene co-expression network analysis (WGCNA) was conducted to identify age-associated co-expression modules. Candidate therapeutics were prioritized using the Genomics of Drug Sensitivity in Cancer (GDSC) resource and evaluated using patient-derived organoids (PDOs). RESULTS: Compared with OMBC, YMBC more frequently had human epidermal growth factor receptor 2 (HER2)-positive status (14.91% vs. 4.02%) and triple-negative tumors (4.92% vs. 1.78%), and had worse 5-year recurrence-free survival (hazard ratio=2.19, P=0.018). Transcriptomic analyses indicated enrichment of neural-related programs and reduced immune-related signaling in YMBC, and xCell/ESTIMATE supported lower immune infiltration. Consistently, WGCNA identified age-associated modules linking neural-related programs with reduced immune infiltration. Immunohistochemistry supported increased perineural invasion and lower CD8+ T cell infiltration in YMBC. GDSC-guided prioritization with PDO testing nominated sepantronium bromide (YM155) as a candidate vulnerability in YMBC. WES showed a higher NBPF10 mutation frequency in YMBC (54.5% vs. 14.3%, P<0.05). CONCLUSIONS: Integrated multi-omics profiling revealed age-stratified clinical and molecular heterogeneity in MBC. YMBC patients demonstrated inferior recurrence-free survival, neural signaling enrichment, an immune-cold microenvironment, and enriched NBPF10 mutations. These findings support age as a meaningful stratification variable in MBC risk assessment and treatment planning, and highlight the need for caution when considering treatment de-escalation in younger patients, while nominating YM155 as a candidate agent for prospective evaluation.

Male breast cancer↗

PubMed2005

Lotus japonicus metabolic profiling. Development of gas chromatography-mass spectrometry resources for the study of plant-microbe interactions.

Symbiotic nitrogen fixation (SNF) in legume root nodules requires differentiation and integration of both plant and bacterial metabolism. Classical approaches of biochemistry, molecular biology, and genetics have revealed many aspects of primary metabolism in legume nodules that underpin SNF. Functional genomics approaches, especially transcriptomics and proteomics, are beginning to provide a more holistic picture of the metabolic potential of nodules in model legumes like Medicago truncatula and Lotus japonicus. To extend these approaches, we have established protocols for nonbiased measurement and analysis of hundreds of metabolites from L. japonicus, using gas chromatography coupled with mass spectrometry. Following creation of mass spectral tag libraries, which represent both known and unknown metabolites, we measured and compared relative metabolite levels in nodules, roots, leaves, and flowers of symbiotic plants. Principal component analysis of the data revealed distinct metabolic phenotypes for the different organs and led to the identification of marker metabolites for each. Metabolites that were enriched in nodules included: octadecanoic acid, asparagine, glutamate, homoserine, cysteine, putrescine, mannitol, threonic acid, gluconic acid, glyceric acid-3-P, and glycerol-3-P. Hierarchical cluster analysis enabled discrimination of 10 groups of metabolites, based on distribution patterns in diverse Lotus organs. The resources and tools described here, together with ongoing efforts in the areas of genome sequencing, and transcriptome and proteome analysis of L. japonicus and Mesorhizobium loti, should lead to a better understanding of nodule metabolism that underpins SNF.

Gas Chromatography-Mass Spectrometry↗

PubMed2006

Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas.

This study analyzed gene expression patterns and global genomic alterations in hepatocellular carcinomas (HCC), hepatoblastomas (HPBL), tissue adjacent to HCC and normal liver tissue derived from normal livers and hepatic resections. We found that HCC and adjacent non-neoplastic cirrhotic tissue have considerable overlap in gene expression patterns compared to normal liver. Several genes including Glypican 3, spondin-2, PEG10, EDIL3 and Osteopontin are over-expressed in HCC vs. adjacent tissue whereas Ficolin 3 is the most consistently under-expressed gene. HCC can be subdivided into three clusters based on gene expression patterns. HCC and HPBL have clearly different patterns of gene expression, with genes IGF2, Fibronectin, DLK1, TGFb1, MALAT1 and MIG6 being over-expressed in HPBL versus HCC. In addition, specific areas of the genome appear unstable in HCC, with the same regions undergoing either deletion or increased gene dosage in all HCC. In conclusion, a set of specific genes and areas of genomic instability are found across the board in liver neoplasia.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Transcriptome analysis of the Mg2+-responsive PhoP regulator in Yersinia pestis.

PhoP was previously shown to be important for Yersinia pestis survival in macrophage and under macrophage-induced stresses. In this work, a phoP disruptant of Y. pestis 201 was generated using the Red cloning procedure. The transcription profile of the wild-type Y. pestis was then compared with that of the phoP mutant under Mg2+-limiting conditions. It was revealed that PhoP/PhoQ governed a wide set of cellular pathways in Y. pestis, especially including the positive regulation of many metabolic processes, Mg2+ transport, peptidoglycan remodeling, lipopolysaccharide (LPS) modification and various stress-protective functions. The Mg2+ transport system regulated by PhoP may make Y. pestis to maintain the magnesium homeostasis under low Mg2+ environments. The PhoP-controlled stress-protective functions likely constitute the molecular basis for the observation that mutation of the phoP gene rendered the bacteria more sensitive to various macrophage-induced stresses. Modification of LPS mediated by PhoP is hypothesized to not only neutralize negative charges as normally done by Mg2+ ions, but also mediate the resistance of Y. pestis to antimicrobial peptides. The microarray results provide a population of candidate genes or pathways, and further biochemical experiments are needed to elucidate the PhoP-dependent mechanisms by which Y. pestis survives the antibacterial strategies employed by host macrophages.

Animals↗

PubMed2003

Cardiac transcriptome analysis in obesity-related hypertension.

Obesity is associated with volumetric arterial hypertension and with early increase in heart rate and decreased heart rate variability. The consequences of obesity-related hypertension on heart gene regulation are poorly known and were investigated in a model of obesity-related hypertension induced by high fat diet in dogs. When compared with control animals (n=6), a 9-week high fat diet (n=6) provoked significant weight gain and increased blood pressure load and heart rate but failed to significantly change left ventricular mass assessed by echocardiography. Subtractive hybridization of dog heart cDNA libraries were used to generate sublibraries containing differentially expressed cDNAs that were in turn spotted onto membranes to create custom microarrays. Hybridizations of these microarrays with complex probes representing mRNAs expressed in right atria and left ventricles from obese hypertensive and control dogs were performed. Thirty-eight differentially expressed genes were identified; altered expression was confirmed by Northern blot analysis in 15. In addition, real-time quantitative polymerase chain reaction confirmed differential expression for 80% of the randomly chosen tested genes. Once identified, transcripts were categorized into groups involved in metabolism, cell signaling, ionic regulation, cell proliferation, protein synthesis, and tissue remodeling. In addition, we found a set of 11 cDNAs encoding proteins with unknown functions. This study clearly shows that obesity-related hypertension, lasting for only 9 weeks, causes marked changes in gene expression in right atrium as well as the left ventricle that may contribute to early functional changes in heart function and to long-term structural changes such as left ventricular hypertrophy and remodeling.

Animals↗

PubMed2026

Zea mays Drought-Overly Sensitive1/TUBA4 Is Wilty3, and Transcriptome Co-Expression Analysis of Shoot Meristem Mutant Tissues Reveals Wilty2/TUB6:Wi3 Interactions Associated With Stem Vascular Bundle Development.

Plant vasculature is essential for the transport of water, nutrients, and signaling molecules across organs, while also providing critical mechanical support for growth and development. Disruptions in vascular bundle formation can therefore lead to severe physiological and developmental defects. In maize, ethyl methanesulfonate (EMS)-induced dominant nonallelic Wilty mutants exhibit a pronounced wilting phenotype even under well-watered conditions, indicating underlying defects in vascular function. In this study, we characterized the Wi3 mutant, identified as ZmDrought-Overly-Sensitive1/DOS1, and compared it with the previously described Wi2 mutant to uncover shared mechanisms underlying their phenotypes. We provide evidence, by bulk segregant resequencing linkage disequilibrium of SNPs adjacent to the causal Wilty SNPs in respective ß- and α-tubulin genes, for the personal communication from Gerry Neuffer that Wi2/ß-tub6 provenance is from ACR-related stock, whereas Wi3/α-tub4 allele is from Mo17, not B73 as claimed by the authors who cloned Dos1. Histochemical staining and Fourier-transform infrared (FTIR) spectroscopy of vascular bundles in Wi3 indicated apparent alterations in cellulose and lignin content consistent with those observed in Wi2. Transcriptome analysis of shoot meristems further indicated that similar sets of genes and pathways are differentially expressed in both mutants, suggesting convergence on common biological pathways. Using bulk-segregant whole-genome resequencing, we identified alpha-tubulin4 (TUA4) as the causal gene in Wi3 (ZmDOS1), harboring a C-to-T substitution within the N-terminal GTPase-binding domain. This mutation results in a glutamic acid196-to-lysine substitution. Given that α- and β-tubulin subunits heterodimerize, and in many plants and animal mutant alleles are dominant-negative gains-of-function, we infer Wi2, Wi3, and likely Wi4, based on very similar FTIR biophysical difference spectra, may act as effectors of vascular bundle cell wall deposition, potentially involving vesicle trafficking as recently shown for asymmetric cell divisions in maize stomatal development. Together, these findings highlight the functional interdependence of tubulin subunits and provide a plausible mechanistic framework for the striking biophysical, transcriptomic, and phenotypic similarities observed between Wi2, Wi3/ZmDOS1, and Wi4 mutants.

bulk segregant analysis↗

PubMed2004

The unique transcriptome through day 3 of human preimplantation development.

Successful human development is dependent upon a cascade of events following fertilization. Unfortunately, knowledge of these critical events in humans is remarkably incomplete. Although hundreds of thousands of human embryos are cultured yearly at infertility centers worldwide, the vast majority fail to develop in culture or following transfer to the uterus. In this study, we sought to characterize global patterns of gene expression in individual, normal embryos during the first three days of embryonic life using microarrays; we then compared gene expression between normally growing and growth-arrested embryos using quantitative PCR. Our results documented several novel findings. First, we found that a complex pattern of gene expression exists; most genes that are transcriptionally modulated during the first three days following fertilization are not upregulated, as was previously thought, but are downregulated. Second, we observed that the majority of genes exhibiting differential expression during preimplantation development are of unknown identity and/or function. Third, we show that embryonic transcriptional programs are clearly established by day 3 following fertilization, even in embryos that arrested prematurely with 2-, 3- or 4-cells. This indicates that failure to activate transcription is not associated with the majority of human preimplantation embryo loss. Finally, taken together, these results provide the first global analysis of the human preimplantation embryo transcriptome, and demonstrate that RNA can be amplified from single oocytes and embryos for analysis by cDNA microarray technology, thus lending credence to additional studies of genetic regulation in these cell types, as well as in other small biological samples.

Blastocyst↗

PubMed2006

Transcriptomic footprints disclose specificity of reactive oxygen species signaling in Arabidopsis.

Reactive oxygen species (ROS) are key players in the regulation of plant development, stress responses, and programmed cell death. Previous studies indicated that depending on the type of ROS (hydrogen peroxide, superoxide, or singlet oxygen) or its subcellular production site (plastidic, cytosolic, peroxisomal, or apoplastic), a different physiological, biochemical, and molecular response is provoked. We used transcriptome data generated from ROS-related microarray experiments to assess the specificity of ROS-driven transcript expression. Data sets obtained by exogenous application of oxidative stress-causing agents (methyl viologen, Alternaria alternata toxin, 3-aminotriazole, and ozone) and from a mutant (fluorescent) and transgenic plants, in which the activity of an individual antioxidant enzyme was perturbed (catalase, cytosolic ascorbate peroxidase, and copper/zinc superoxide dismutase), were compared. In total, the abundance of nearly 26,000 transcripts of Arabidopsis (Arabidopsis thaliana) was monitored in response to different ROS. Overall, 8,056, 5,312, and 3,925 transcripts showed at least a 3-, 4-, or 5-fold change in expression, respectively. In addition to marker transcripts that were specifically regulated by hydrogen peroxide, superoxide, or singlet oxygen, several transcripts were identified as general oxidative stress response markers because their steady-state levels were at least 5-fold elevated in most experiments. We also assessed the expression characteristics of all annotated transcription factors and inferred new candidate regulatory transcripts that could be responsible for orchestrating the specific transcriptomic signatures triggered by different ROS. Our analysis provides a framework that will assist future efforts to address the impact of ROS signals within environmental stress conditions and elucidate the molecular mechanisms of the oxidative stress response in plants.

Arabidopsis↗

PubMed2026

Gene expression profiling identifies potential biomarkers for vaso-occlusive episodes in sickle cell disease.

Vaso-occlusive episodes (VOEs) or acute pain events, involving complex interactions between sickle erythrocytes and other blood cells, are a hallmark of sickle cell disease (SCD). In this study, we analyzed changes in peripheral blood transcriptomes between steady state and VOEs in individuals with SCD. We followed a cohort of 174 individuals with SCD with or without chronic pain and collected peripheral blood at clinic visits (steady state) and during hospitalizations (VOEs). We performed RNA-Seq profiling of CD45+ leukocytes and CD71+ erythroid cells. Pathways linked to complement activation, coagulation, and IL-6/JAK/STAT3 signaling were enriched during VOEs in the CD45+ cells. Contrastingly, the CD71+ cells showed an enrichment of pathways related to the cell cycle, such as mTORC1 signaling and the G2M checkpoint during VOEs. We then analyzed the expression changes of genes in patients with longitudinal data to determine potential biomarkers for VOEs. Expression of 4 genes - FAM20A, IL1B, MS4A4A, and SERPINB2 - was elevated during VOEs compared with steady state in the majority of patients. Furthermore, our results indicate that patients experiencing chronic pain exhibited 44% increased enrichment of significant pathways during VOEs when compared with patients without chronic pain.

Humans↗

PubMed2007

Widespread mRNA polyadenylation events in introns indicate dynamic interplay between polyadenylation and splicing.

mRNA polyadenylation and pre-mRNA splicing are two essential steps for the maturation of most human mRNAs. Studies have shown that some genes generate mRNA variants involving both alternative polyadenylation and alternative splicing. Polyadenylation in introns can lead to conversion of an internal exon to a 3' terminal exon, which is termed composite terminal exon, or usage of a 3' terminal exon that is otherwise skipped, which is termed skipped terminal exon. Using cDNA/EST and genome sequences, we identified polyadenylation sites in introns for all currently known human genes. We found that approximately 20% human genes have at least one intronic polyadenylation event that can potentially lead to mRNA variants, most of which encode different protein products. The conservation of human intronic poly(A) sites in mouse and rat genomes is lower than that of poly(A) sites in 3'-most exons. Quantitative analysis of a number of mRNA variants generated by intronic poly(A) sites suggests that the intronic polyadenylation activity can vary under different cellular conditions for most genes. Furthermore, we found that weak 5' splice site and large intron size are the determining factors controlling the usage of composite terminal exon poly(A) sites, whereas skipped terminal exon poly(A) sites tend to be associated with strong polyadenylation signals. Thus, our data indicate that dynamic interplay between polyadenylation and splicing leads to widespread polyadenylation in introns and contributes to the complexity of transcriptome in the cell.

Animals↗

PubMed2005

Laterally transferred elements and high pressure adaptation in Photobacterium profundum strains.

BACKGROUND: Oceans cover approximately 70% of the Earth's surface with an average depth of 3800 m and a pressure of 38 MPa, thus a large part of the biosphere is occupied by high pressure environments. Piezophilic (pressure-loving) organisms are adapted to deep-sea life and grow optimally at pressures higher than 0.1 MPa. To better understand high pressure adaptation from a genomic point of view three different Photobacterium profundum strains were compared. Using the sequenced piezophile P. profundum strain SS9 as a reference, microarray technology was used to identify the genomic regions missing in two other strains: a pressure adapted strain (named DSJ4) and a pressure-sensitive strain (named 3TCK). Finally, the transcriptome of SS9 grown under different pressure (28 MPa; 45 MPa) and temperature (4 degrees C; 16 degrees C) conditions was analyzed taking into consideration the differentially expressed genes belonging to the flexible gene pool. RESULTS: These studies indicated the presence of a large flexible gene pool in SS9 characterized by various horizontally acquired elements. This was verified by extensive analysis of GC content, codon usage and genomic signature of the SS9 genome. 171 open reading frames (ORFs) were found to be specifically absent or highly divergent in the piezosensitive strain, but present in the two piezophilic strains. Among these genes, six were found to also be up-regulated by high pressure. CONCLUSION: These data provide information on horizontal gene flow in the deep sea, provide additional details of P. profundum genome expression patterns and suggest genes which could perform critical functions for abyssal survival, including perhaps high pressure growth.

Atmospheric Pressure↗

PubMed2025

A pluripotent stem cell atlas of multilineage differentiation.

Human pluripotent stem cells offer a scalable platform to study genetic and signalling mechanisms governing cell lineage decisions during differentiation. Genome-wide and single-cell transcriptomics technologies likewise offer high-throughput analysis of heterogeneous cell differentiation states. While in vivo development has been extensively characterised using these technologies, there remains a need for comprehensive single-cell transcriptomic profiling of stem cell differentiation from pluripotency. Understanding gene expression changes governing differentiation in vitro is key to developing high fidelity differentiation protocols and understanding fundamental mechanisms of development. We generated a single-cell RNA sequencing time course to study the role of developmental signalling pathways on multilineage diversification from pluripotency in vitro. The combined dataset of over 60,000 cells spans cell types from a time course of differentiation across all germ layers, ranging from gastrulation cell states to progenitor and committed cell types. These data provide a diverse benchmarking reference point to compare against in vivo development and advance understanding of signalling regulation of differentiation, providing insights into protocol development, drug screening, and regenerative medicine applications.

Pluripotent Stem Cells↗

PubMed2026

Mechanism of Action of Hedyotis diffusa Extract in a Rat Model of Acute Lung Injury Based on Transcriptomic Analysis.

OBJECTIVE: This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following Hedyotis diffusa water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE. METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly divided into six groups: Control group, ALI group, DXMS group, HDWE-L group (100 mg/kg), HDWE-M group (200 mg/kg), and HDWE-H group (300 mg/kg). Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to evaluate lung pathological changes and collagen deposition. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α TNF-α interleukin-1β IL-1β, erleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Transcriptomic analysis identified differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), receiver operating characteristic (ROC), and immune infiltration analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) detected the mRNA expression levels of SPHK1, RELA, and NFKBIA. Immunohistochemistry evaluated the expression of eight hub targets, including endothelin-1 (EDN1), sphingosine kinase 1 (SPHK1), intercellular adhesion molecule 1 (ICAM1), interleukin-17 (IL-17), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), NF-κB p65 (encoded by RELA), WT1-associated protein (WTAP), and myeloperoxidase (MPO). UHPLC-Q-Orbitrap HRMS characterized HDWE constituents. Molecular docking analysis was performed between 22 compounds and eight hub targets, followed by 100 ns molecular dynamics simulations and molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) binding free energy calculations for five core targets. Compared with the control group, the ALI group showed increased levels of TNF-α (86%), IL-1β (107%), and IL-6 (66%), accompanied by a 43% reduction in IL-10 and a 300% increase in lung collagen deposition. All HDWE doses alleviated inflammatory responses, with medium-dose HDWE showing the most pronounced effects. Specifically, medium-dose HDWE increased IL-10 levels by 52% and reduced IL-6, TNF-α, and IL-1β levels by 18%, 22%, and 11%, respectively. Transcriptomic analysis identified 2512 DEGs between the control group and ALI groups, 832 exclusive DEGs between the ALI group and HDWE-M groups, and 876 overlapping DEGs enriched in TNF, IL-17, and NF-κB signaling pathways. The eight-hub-gene diagnostic model achieved an area under the curve (AUC) of 0.969. RELA, SPHK1, and four other hub genes showed positive correlations with Th1, Th17, and neutrophil infiltration. In the ALI group, SPHK1, RELA, and NFKBIA mRNA expression levels were 1.30-, 0.96-, and 0.71-fold of those in the control group, respectively. Compared with the ALI group, high-dose HDWE treatment and low-dose HDWE treatment reduced SPHK1 expression to 0.62- and 0.57-fold, respectively, and increased NFKBIA expression to 1.68- and 1.58-fold, respectively. High-dose HDWE treatment reduced RELA expression to 0.43-fold. The expression levels of inflammation-related proteins were increased in the ALI group and were reduced after HDWE treatment. Twenty-two HDWE components were identified, 16 of which met the docking criteria. Asperulosidic acid exhibited favorable predicted binding affinities with all eight targets, with calculated binding free energies of -14.74, -14.92, -17.58, -23.04, and -16.10 kcal/mol for MPO, IL-17, NF-κB p65, PTGS2/COX-2, and SPHK1, respectively. CONCLUSIONS: This study provides systematic in vivo pharmacodynamic and in silico component-target evidence regarding the protective effects of HDWE against LPS-induced ALI. HDWE treatment increased NFKBIA expression and reduced SPHK1, RELA, and multiple inflammatory protein levels, suggesting that HDWE may regulate the IL-17/NF-κB-associated inflammatory network, although direct causal relationships require further validation. Asperulosidic acid may represent a key bioactive component with broad target-binding potential. This study was limited by the use of an LPS-induced rat ALI model without gene knockout or target inhibitor validation; therefore, further functional experiments are required to confirm the proposed regulatory mechanisms.

Hedyotis diffusa↗

PubMed2025

Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function.

BACKGROUND: Advanced gastric cancer (GC) exhibits a high recurrence rate and a dismal prognosis. Myocyte enhancer factor 2c (MEF2C) was found to contribute to the development of various types of cancer. Therefore, our aim is to develop a prognostic model that predicts the prognosis of GC patients and initially explore the role of MEF2C in immunotherapy for GC. METHODS: Transcriptome sequence data of GC was obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and PRJEB25780 cohort for subsequent immune infiltration analysis, immune microenvironment analysis, consensus clustering analysis and feature selection for definition and classification of gene M and N. Principal component analysis (PCA) modeling was performed based on gene M and N for the calculation of immune checkpoint inhibitor (ICI) Score. Then, a Nomogram was constructed and evaluated for predicting the prognosis of GC patients, based on univariate and multivariate Cox regression. Functional enrichment analysis was performed to initially investigate the potential biological mechanisms. Through Genomics of Drug Sensitivity in Cancer (GDSC) dataset, the estimated IC50 values of several chemotherapeutic drugs were calculated. Tumor-related transcription factors (TFs) were retrieved from the Cistrome Cancer database and utilized our model to screen these TFs, and weighted correlation network analysis (WGCNA) was performed to identify transcription factors strongly associated with immunotherapy in GC. Finally, 10 patients with advanced GC were enrolled from Sun Yat-sen University Cancer Center, including paired tumor tissues, paracancerous tissues and peritoneal metastases, for preparing sequencing library, in order to perform external validation. RESULTS: Lower ICI Score was correlated with improved prognosis in both the training and validation cohorts. First, lower mutant-allele tumor heterogeneity (MATH) was associated with lower ICI Score, and those GC patients with lower MATH and lower ICI Score had the best prognosis. Second, regardless of the T or N staging, the low ICI Score group had significantly higher overall survival (OS) compared to the high ICI Score group. For its mechanisms, consistently, for Camptothecin, Doxorubicin, Mitomycin, Docetaxel, Cisplatin, Vinblastine, Sorafenib and Paclitaxel, all of the IC50 values were significantly lower in the low ICI Score group compared to the high ICI Score group. As a result, based on univariate and multivariate Cox regression, ICI Score was considered to be an independent prognostic factor for GC. And our Nomogram showed good agreement between predicted and actual probabilities. Based on CIBERSORT deconvolution analysis, there was difference of immune cell composition found between high and low ICI Score groups, probably affecting the efficacy of immunotherapy. Then, MEF2C, a tumor-related transcription factor, was screened out by WGCNA analysis. Higher MEF2C expression is significantly correlated with a worse OS. Moreover, its higher expression is also negatively correlated with tumor mutation burden (TMB) and microsatellite instability (MSI), but positively correlated with several immunosuppressive molecules, indicating MEF2C may exert its influence on tumor development by upregulating immunosuppressive molecules. Finally, based on transcriptome sequencing data on 10 paired tumor tissues from Sun Yat-sen University Cancer Center, MEF2C expression was significantly lower in paracancerous tissues compared to tumor tissues and peritoneal metastases, and it was also lower in tumor tissues compared to peritoneal metastases, indicating a potential positive association between MEF2C expression and tumor invasiveness. CONCLUSIONS: Our prognostic model can effectively predict outcomes and facilitate stratification GC patients, offering valuable insights for clinical decision-making. The identified transcription factor MEF2C can serve as a biomarker for assessing the efficacy of immunotherapy for GC.

Humans↗

PubMed2026

Impaired leptin A signaling disrupts hepatic lipid metabolism and growth in female medaka (Oryzias latipes).

Leptin is a central regulator of appetite and energy metabolism in vertebrates, and its deficiency in mammals typically results in hyperphagia and severe obesity. In fish, however, the physiological roles of leptin remain less clearly defined, partly due to the whole genome duplication (WGD) and divergent expression patterns. In this study, we generated a leptin A (lepa) loss-of-function mutant in medaka (Oryzias latipes) using CRISPR/Cas9 to investigate the function of leptin signaling. Phenotypic analysis revealed that female homozygous mutants exhibited significantly reduced body length and body weight compared with wild-type females, indicating growth impairment. Unexpectedly, despite their lean phenotype, the female mutants developed pronounced hepatic steatosis accompanied by the formation of spongiosis hepatis structures, while no obvious fibrosis was detected. To explore the molecular mechanisms underlying these abnormalities, transcriptomic profiling of mutant livers was performed. Differentially expressed genes were significantly enriched in pathways related to lipid metabolism, including Fatty acid metabolism and PPAR signaling pathway, suggesting a potential reduction in hepatic fatty acid β-oxidation capacity. In addition, genes involved in endoplasmic reticulum stress, autophagy, and apoptosis were altered, indicating transcriptional changes in cellular stress-response pathways under leptin A deficiency. Together, these findings suggest that leptin A may play an important role in coordinating growth and hepatic lipid metabolism in medaka and highlight potential differences in leptin-mediated metabolic regulation between fish and mammals.

Animals↗

PubMed2026

Evolution and Expression Divergence of Legume PAL Genes Suggest Associations with Drought Response and Root Nodule Development.

Comparative genomic analyses provide insight into the mechanisms underlying gene-family evolution and crop adaptation. Here, we used the legume phenylalanine ammonia-lyase (PAL) gene family as a model and integrated pan-genomic, phylogenetic, molecular evolutionary, duplication-mode, and transcriptomic analyses, while developing GFtool for gene family identification. Across 45 genomes, we identified 302 PAL genes and classified them into five Groups. Groups 1-3 represented ancient lineages shared with outgroups, whereas Groups 4 and 5 were legume-specific. Molecular-clock analyses placed the divergence of Group 2 near the Paleocene-Eocene transition, while Groups 4 and 5 diversified from the middle Eocene to the early Oligocene. WGD/segmental duplication broadly contributed to PAL copy-number expansion, whereas tandem duplication was enriched in Group 5 of Papilionoideae. Group 2 genes showed drought-induced expression, whereas Group 5 genes were associated with early root nodule development. GFtool provides a scalable framework for gene-family studies.

Fabaceae↗