Mammary fat globules as a source of mRNA to model alterations in the expression of some milk component genes during lactation in bovines.

BACKGROUND: The milk's nutritional value is determined by its constituents, including fat, protein, carbohydrates, and minerals. The mammary gland's ability to produce milk is controlled by a complex network of genes. Thereby, the fat, protein, and lactose synthesis must be boost in milk to increase milk production efficiency. This can be accomplished by fusing genetic advancements with proper management practices. Therefore, this study aimed to investigate the association between the Lipoprotein lipase (LPL), kappa casein CSN3, and Glucose transporter 1 (GLUT1) genes expression levels and such milk components as fat, protein, and lactose in different dairy breeds during different stages of lactation. METHODS: To achieve such a purpose, 94 milk samples were collected (72 samples from 36 multiparous black-white and red-white Holstein-Friesian (HF) cows and 22 milk samples from 11 Egyptian buffaloes) during the early and peak lactation stages. The milk samples were utilized for milk analysis and genes expressions analyses using non- invasive approach in obtaining milk fat globules (MFGs) as a source of Ribonucleic acid (RNA). RESULTS: LPL and CSN3 genes expressions levels were found to be significantly higher in Egyptian buffalo than Holstein-Friesian (HF) cows as well as fat and protein percentages. On the other hand, GLUT1 gene expression level was shown to be significantly higher during peak lactation than early lactation. Moreover, lactose % showed a significant difference in peak lactation phase compared to early lactation phase. Also, fat and protein percentages were significantly higher in early lactation period than peak lactation period but lactose% showed the opposite pattern of Egyptian buffalo. CONCLUSION: Total RNA can be successfully obtained from MFGs. The results suggest that these genes play a role in glucose absorption and lactose synthesis in bovine mammary epithelial cells during lactation. Also, these results provide light on the differential expression of these genes among distinct Holstein-Friesian cow breeds and Egyptian buffalo subspecies throughout various lactation phases.

Surviving extreme radiation.

Tiny animals known as tardigrades use a combination of DNA repair machinery and a novel protein to mend their genome after intense ionizing radiation.

Transcriptome analysis of avian livers reveals different molecular changes to three urban pollutants: Soot, artificial light at night and noise.

Identifying key molecular pathways and genes involved in the response to urban pollutants is an important step in furthering our understanding of the impact of urbanisation on wildlife. The expansion of urban habitats and the associated human-introduced environmental changes are considered a global threat to the health and persistence of humans and wildlife. The present study experimentally investigates how short-term exposure to three urban-related pollutants -soot, artificial light at night (ALAN) and traffic noise-affects transcriptome-wide gene expression in livers from captive female zebra finches (Taeniopygia guttata). Compared to unexposed controls, 17, 52, and 28 genes were differentially expressed in soot, ALAN and noise-exposed birds, respectively. In soot-exposed birds, the enriched gene ontology (GO) terms were associated with a suppressed immune system such as interferon regulating genes (IRGs) and responses to external stimuli. For ALAN-exposed birds, enriched GO terms were instead based on downregulated genes associated with detoxification, redox, hormonal-, and metabolic processes. Noise exposure resulted in downregulation of genes associated with the GO terms: cellular responses to substances, catabolic and cytokine responses. Among the individually differentially expressed genes (DEGs), soot led to an increased expression of genes related to tumour progression. Likewise, ALAN revealed an upregulation of multiple genes linked to different cancer types. Both sensory pollutants (ALAN and noise) led to increased expression of genes linked to neuronal function. Interestingly, noise caused upregulation of genes associated with serotonin regulation and function (SLC6A4 and HTR7), which previous studies have shown to be under selection in urban birds. These outcomes indicate that short-term exposure to the three urban pollutants perturbate the liver transcriptome, but most often in different ways, which highlights future studies of multiple-stress exposure and their interactive effects, along with their long-term impacts for urban-dwelling wildlife.

Behavioral, biochemical, histopathological evaluation and gene expression of brain injury induced by nanoceria injected intranasal or intraperitoneal in mice.

Background: Nanotechnology has shown a remarkable progress nevertheless, there is a growing concern about probable neurotoxic and neurodegenerative effects due to NPs exposure. Various toxicological and epidemiological studies reported that the brain is a main target for ultrafine particles. Brain inflammation is considered as a possible mechanism that can participate to neurotoxic and neurodegenerative effects. Whether nanoparticles (NPs) may produce neurotoxicity and promote neurodegenerative is largely unstudied. The present study was done to investigate whether intranasal and intra-peritoneal exposure to cerium oxide nanoparticles (CeO2NPs, nanoceria (NC)) could cause neurotoxicity and neurodegenerative changes in the brain tissue through conducting some behavioral tests, biochemical evaluation, histopathological examinations of brain hippocampus and gene expressions. Method: Fifteen mice were separated into 3 equal groups. In group (I) "control group", mice were received distilled water orally and kept as a control group. Mice in the group (II) "NC I/P group" were injected i.p with cerium oxide nanoparticles at a dose of 40 mg/kg b.wt, twice weekly for 3 weeks. In group (III) "NC I/N group" mice were received nanoceria intranasally (40 mg/kg b.wt), twice weekly for 3 weeks. Results: Exposure to nanceria resulted in oxidative damage in brain tissue, a significant increase in malondialdehyde (MDA) and acetylcholinestrase (AchE) levels, significant decrease in reduced glutathione (GSH) concentration, upregulation in the apoptosis-related genes (c-Jun: c-Jun N-terminal kinases (JNKs), c-Fos: Fos protooncogene, AP-1 transcription factor subunit, c-Myc: c-myelocytomatosis oncogene product or MYC protooncogene, bHLH transcription factor), locomotor and cognitive impairment in mice but the effect was more obvious when nanoceria adminstred intraperitoneally. Conculsion: Nanoceria cause oxidative damage in brain tissue of mice when adminstred nanoceria intraperitoneally more than those received nanoceria intranasal.

The whole transcriptome analysis using FFPE and fresh tissue samples identifies the molecular fingerprint of osteosarcoma.

Osteosarcoma is a form of bone cancer that predominantly impacts osteoblasts, the cells responsible for creating fresh bone tissue. Typical indications include bone pain, inflammation, sensitivity, mobility constraints, and fractures. Utilising imaging techniques such as X-rays, MRI scans, and CT scans can provide insights into the size and location of the tumour. Additionally, a biopsy is employed to confirm the diagnosis. Analysing genes with distinct expression patterns unique to osteosarcoma can be valuable for early detection and the development of effective treatment approaches. In this research, we comprehensively examined the entire transcriptome and pinpointed genes with altered expression profiles specific to osteosarcoma. The study mainly aimed to identify the molecular fingerprint of osteosarcoma. In this study, we processed 90 FFPE samples from PathWest with an almost equal number of osteosarcoma and healthy tissues. RNA was extracted from Paraffin-embedded tissue; RNA was sequenced, the sequencing data was analysed, and gene expression was compared to the healthy samples of the same patients. Differentially expressed genes in osteosarcoma-derived samples were identified, and the functions of those genes were explored. This result was combined with our previous studies based on FFPE and fresh samples to perform a meta-analysis. We identified 1,500 identical differentially expressed genes in PathWest osteosarcoma samples compared to normal tissue samples of the same patients. Meta-analysis with combined fresh tissue samples identified 530 differentially expressed genes. IFITM5, MMP13, PANX3, and MAGEA6 were some of the most overexpressed genes in osteosarcoma samples, while SLC4A1, HBA1, HBB, AQP7 genes were some of the top downregulated genes. Through the meta-analysis, 530 differentially expressed genes were identified to be identical among FFPE (105 FFPE samples) and 36 fresh bone samples. Deconvolution analysis with single-cell RNAseq data confirmed the presence of specific cell clusters in FFPE samples. We propose these 530 DEGs as a molecular fingerprint of osteosarcoma.

Genome-wide Methylation Dynamics and Context-dependent Gene Expression Variability in Differentiating Preadipocytes.

Obesity, characterized by the accumulation of excess fat, is a complex condition resulting from the combination of genetic and epigenetic factors. Recent studies have found correspondence between DNA methylation and cell differentiation, suggesting a role of the former in cell fate determination. There is a lack of comprehensive understanding concerning the underpinnings of preadipocyte differentiation, specifically when cells are undergoing terminal differentiation (TD). To gain insight into dynamic genome-wide methylation, 3T3 L1 preadipocyte cells were differentiated by a hormone cocktail. The genomic DNA was isolated from undifferentiated cells and 4 hours, 2 days postdifferentiated cells, and 15 days TD cells. We employed whole-genome bisulfite sequencing (WGBS) to ascertain global genomic DNA methylation alterations at single base resolution as preadipocyte cells differentiate. The genome-wide distribution of DNA methylation showed similar overall patterns in pre-, post-, and terminally differentiated adipocytes, according to WGBS analysis. DNA methylation decreases at 4 hours after differentiation initiation, followed by methylation gain as cells approach TD. Studies revealed novel differentially methylated regions (DMRs) associated with adipogenesis. DMR analysis suggested that though DNA methylation is global, noticeable changes are observed at specific sites known as "hotspots." Hotspots are genomic regions rich in transcription factor (TF) binding sites and exhibit methylation-dependent TF binding. Subsequent analysis indicated hotspots as part of DMRs. The gene expression profile of key adipogenic genes in differentiating adipocytes is context-dependent, as we found a direct and inverse relationship between promoter DNA methylation and gene expression.

Modulation in the ratio of abscisic acid to gibberellin level determines genetic variation of seed dormancy in barley (Hordeum vulgare L.).

Abscisic acid (ABA) and gibberellin (GA) are major regulators of seed dormancy, an adaptive trait closely associated with preharvest sprouting. This study examined transcriptional regulation of ABA and GA metabolism genes and modulation of ABA and GA levels in seeds of barley genotypes exhibiting a range of dormancy phenotype. We observed a very strong negative correlation between genetic variation in seed germination and embryonic ABA level (r = 0.85), which is regulated by transcriptional modulation of HvNCED1 and/or HvCYP707A genes. A strong positive correlation was evident between variation in seed germination and GA level (r = 0.64), mediated via transcriptional regulation of GA biosynthesis genes, HvGA20ox2 and/or HvGA3oxs, and GA catabolism genes, HvGA2ox3 and/or HvGA3ox6. Modulation of the ABA and GA levels in the genotypes led to the prevalence of ABA to GA level ratio that exhibited a very strong negative correlation (r = 0.84) with seed germination, highlighting the importance of a shift in ABA/GA ratio in determining genetic variation of dormancy in barley seeds. Our results overall show that transcriptional regulation of specific ABA and GA metabolism genes underlies genetic variation in ABA/GA ratio and seed dormancy, reflecting the potential use of these genes as molecular tools for enhancing preharvest sprouting resistance in barley.

Interplay of RNA-binding proteins controls germ cell development in zebrafish.

The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants, called germ plasm, confer germline fate in the early embryo. Extensive studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell development. RNA-binding proteins, acting in concert with other germ plasm components, play essential roles in the organization of the germ plasm and the specification, migration, maintenance, and differentiation of primordial germ cells. The loss of their functions impairs germ cell formation and causes sterility or sexual conversion. Evidence is emerging that they instruct germline development through differential regulation of mRNA fates in somatic and germ cells. However, the challenge remains to decipher the complex interplay of maternal germ plasm components in germ plasm compartmentalization and germ cell specification. Since failure to control the developmental outcome of germ cells disrupts the formation of gametes, it is important to gain a complete picture of regulatory mechanisms operating in the germ cell lineage. This review sheds light on the contributions of RNA-binding proteins to germ cell development in zebrafish and highlights intriguing questions that remain open for future investigation.

Expression and function identification of senescence-associated genes under continuous drought treatment in grapevine (Vitis vinifera L.) leaves.

Natural leaf senescence is critical for plant fitness. Drought-induced premature leaf senescence affects grape yield and quality. However, reports on the regulatory mechanisms underlying premature leaf senescence under drought stress are limited. In this study, two-year-old potted 'Muscat Hamburg' grape plants were subjected to continuous natural drought treatment until mature leaves exhibited senescence symptoms. Physiological and biochemical indices related to drought stress and senescence were monitored. Transcriptome and transgenic Arabidopsis were used to perform expression analyses and functional identification of drought-induced senescence-associated genes. Twelve days of continuous drought stress was sufficient to cause various physiological disruptions and visible senescence symptoms in mature 'Muscat Hamburg' leaves. These disruptions included malondialdehyde and H2O2 accumulation, and decreased catalase activity and chlorophyll (Chl) levels. Transcriptome analysis revealed that most genes involved in photosynthesis and Chl synthesis were downregulated after 12 d of drought treatment. Three key Chl catabolic genes (SGR, NYC1, and PAO) were significantly upregulated. Overexpression of VvSGR in wild Arabidopsis further confirmed that SGR directly promoted early yellowing of cotyledons and leaves. In addition, drought treatment decreased expression of gibberellic acid signaling repressors (GAI and GAI1) and cytokinin signal components (AHK4, AHK2, RR22, RR9-1, RR9-2, RR6, and RR4) but significantly increased the expression of abscisic acid, jasmonic acid, and salicylic acid signaling components and responsive transcription factors (bZIP40/ABF2, WRKY54/75/70, ANAC019, and MYC2). Moreover, some NAC members (NAC0002, NAC019, and NAC048) may also be drought-induced senescence-associated genes. These results provide extensive information on candidate genes involved in drought-induced senescence in grape leaves. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01465-2.

Real-world comprehensive genomic and immune profiling reveals distinct age- and sex-based genomic and immune landscapes in tumors of patients with non-small cell lung cancer.

Introduction: Younger patients with non-small cell lung cancer (NSCLC) (<50 years) represent a significant patient population with distinct clinicopathological features and enriched targetable genomic alterations compared to older patients. However, previous studies of younger NSCLC suffer from inconsistent findings, few studies have incorporated sex into their analyses, and studies targeting age-related differences in the tumor immune microenvironment are lacking. Methods: We performed a retrospective analysis of 8,230 patients with NSCLC, comparing genomic alterations and immunogenic markers of younger and older patients while also considering differences between male and female patients. We defined older patients as those ≥65 years and used a 5-year sliding threshold from <45 to <65 years to define various groups of younger patients. Additionally, in an independent cohort of patients with NSCLC, we use our observations to inform testing of the combinatorial effect of age and sex on survival of patients given immunotherapy with or without chemotherapy. Results: We observed distinct genomic and immune microenvironment profiles for tumors of younger patients compared to tumors of older patients. Younger patient tumors were enriched in clinically relevant genomic alterations and had gene expression patterns indicative of reduced immune system activation, which was most evident when analyzing male patients. Further, we found younger male patients treated with immunotherapy alone had significantly worse survival compared to male patients ≥65 years, while the addition of chemotherapy reduced this disparity. Contrarily, we found younger female patients had significantly better survival compared to female patients ≥65 years when treated with immunotherapy plus chemotherapy, while treatment with immunotherapy alone resulted in similar outcomes. Discussion: These results show the value of comprehensive genomic and immune profiling (CGIP) for informing clinical treatment of younger patients with NSCLC and provides support for broader coverage of CGIP for younger patients with advanced NSCLC.

A Critical Review of the Impact of Candidate Copy Number Variants on Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder (NDD) influenced by genetic, epigenetic, and environmental factors. Recent advancements in genomic analysis have shed light on numerous genes associated with ASD, highlighting the significant role of both common and rare genetic mutations, as well as copy number variations (CNVs), single nucleotide polymorphisms (SNPs) and unique de novo variants. These genetic variations disrupt neurodevelopmental pathways, contributing to the disorder's complexity. Notably, CNVs are present in 10%-20% of individuals with autism, with 3%-7% detectable through cytogenetic methods. While the role of submicroscopic CNVs in ASD has been recently studied, their association with genomic loci and genes has not been thoroughly explored. In this review, we focus on 47 CNV regions linked to ASD, encompassing 1,632 genes, including protein-coding genes and long non-coding RNAs (lncRNAs), of which 659 show significant brain expression. Using a list of ASD-associated genes from SFARI, we detect 17 regions harboring at least one known ASD-related protein-coding gene. Of the remaining 30 regions, we identify 24 regions containing at least one protein-coding gene with brain-enriched expression and a nervous system phenotype in mouse mutants, and one lncRNA with both brain-enriched expression and upregulation in iPSC to neuron differentiation. This review not only expands our understanding of the genetic diversity associated with ASD but also underscores the potential of lncRNAs in contributing to its etiology. Additionally, the discovered CNVs will be a valuable resource for future diagnostic, therapeutic, and research endeavors aimed at prioritizing genetic variations in ASD.

GATA2 deficiency syndrome: A compensatory mechanism gone awry?

In their paper, using zebrafish models, Gioacchino et al. have demonstrated the GATA2 haploinsufficiency, the genetic hallmark of GATA2 deficiency syndrome, promotes erythroid and myeloid cytopenia, and have discovered a self-regulatory mechanism to compensate GATA2 levels and protein function. Commentary on: Gioacchino et al. GATA2 heterozygosity causes an epigenetic feedback mechanism resulting in myeloid and erythroid dysplasia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19585.

Functional Analysis of Seed Dormancy Genes by Biolistic Transient Gene Expression in Immature Embryos of Wheat.

Seed dormancy genes typically suppress germination and cell division. Therefore, overexpressing these genes can negatively affect tissue culture, interfering with the generation of transgenic plants and thus hampering the analysis of gene function. Transient expression in target cells is a useful approach for studying the function of seed dormancy genes. Here, we describe a protocol for transiently expressing genes related to seed dormancy in the scutellum of immature wheat (Triticum aestivum) embryos to analyze their effects on germination.

DIGEP-Pred 2.0: A web application for predicting drug-induced cell signaling and gene expression changes.

The analysis of drug-induced gene expression profiles (DIGEP) is widely used to estimate the potential therapeutic and adverse drug effects as well as the molecular mechanisms of drug action. However, the corresponding experimental data is absent for many existing drugs and drug-like compounds. To solve this problem, we created the DIGEP-Pred 2.0 web application, which allows predicting DIGEP and potential drug targets by structural formula of drug-like compounds. It is based on the combined use of structure-activity relationships (SARs) and network analysis. SAR models were created using PASS (Prediction of Activity Spectra for Substances) technology for data from the Comparative Toxicogenomics Database (CTD), the Connectivity Map (CMap) for the prediction of DIGEP, and PubChem and ChEMBL for the prediction of molecular mechanisms of action (MoA). Using only the structural formula of a compound, the user can obtain information on potential gene expression changes in several cell lines and drug targets, which are potential master regulators responsible for the observed DIGEP. The mean accuracy of prediction calculated by leave-one-out cross validation was 86.5 % for 13377 genes and 94.8 % for 2932 proteins (CTD data), and it was 97.9 % for 2170 MoAs. SAR models (mean accuracy-87.5 %) were also created for CMap data given on MCF7, PC3, and HL60 cell lines with different threshold values for the logarithm of fold changes: 0.5, 0.7, 1, 1.5, and 2. Additionally, the data on pathways (KEGG, Reactome), biological processes of Gene Ontology, and diseases (DisGeNet) enriched by the predicted genes, together with the estimation of target-master regulators based on OmniPath data, is also provided. DIGEP-Pred 2.0 web application is freely available at https://www.way2drug.com/digep-pred.

Widespread changes to the translational landscape in a maize microRNA biogenesis mutant.

MicroRNAs are short, non-coding RNAs that repress gene expression in both plants and animals and have diverse functions related to growth, development, and stress responses. The ribonuclease, DICER-LIKE1 (DCL1) is required for two steps in plant miRNA biogenesis: cleavage of the primary miRNAs (pri-miRNAs) to release a hairpin structure, called the precursor miRNA (pre-miRNA) and cleavage of the pre-miRNA to generate the miRNA/miRNA* duplex. The mature miRNA guides the RNA-induced silencing complex to target RNAs with complementary sequences, resulting in translational repression and/or RNA cleavage of target mRNAs. However, the relative contribution of translational repression versus mRNA degradation by miRNAs remains unknown at the genome-level in crops, especially in maize. The maize fuzzy tassel (fzt) mutant contains a hypomorphic mutation in DCL1 resulting in broad developmental defects. While most miRNAs are reduced in fzt, the levels of miRNA-targeted mRNAs are not dramatically increased, suggesting that translational regulation by miRNAs may be common. To gain insight into the repression mechanism of plant miRNAs, we combined ribosome profiling and RNA-sequencing to globally survey miRNA activities in maize. Our data indicate that translational repression contributes significantly to regulation of most miRNA targets and that approximately one-third of miRNA targets are regulated primarily at the translational level. Surprisingly, ribosomes appear altered in fzt mutants suggesting that DCL1 may also have a role in ribosome biogenesis. Thus, DICER-LIKE1 shapes the translational landscape in plants through both miRNA-dependent and miRNA-independent mechanisms.

Effect of ozone treatment on phenylpropanoid metabolism in harvested cantaloupes.

Phenylpropanoid metabolism plays an important role in cantaloupe ripening and senescence, but the mechanism of ozone regulation on phenylpropanoid metabolism remains unclear. This study investigated how ozone treatment modulates the levels of secondary metabolites associated with phenylpropanoid metabolism, the related enzyme activities, and gene expression in cantaloupe. Treating cantaloupes with 15 mg/m3 of ozone after precooling can help maintain postharvest hardness. This treatment also enhances the production and accumulation of secondary metabolites, such as total phenols, flavonoids, and lignin. These metabolites are essential components of the phenylpropanoid metabolic pathway, activating enzymes like phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, 4CL, chalcone synthase, and chalcone isomerase. The results of the transcriptional expression patterns showed that differential gene expression related to phenylpropanoid metabolism in the peel of ozone-treated cantaloupes was primarily observed during the middle and late storage stages. In contrast, the pulp exhibited significant differential gene expression mainly during the early storage stage. Furthermore, it was observed that the level of gene expression in the peel was generally higher than that in the pulp. The correlation between the relative amount of gene changes in cantaloupe, activity of selected enzymes, and concentration of secondary metabolites could be accompanied by positive regulation of the phenylpropanoid metabolic pathway. Therefore, ozone stress induction positively enhances the biosynthesis of flavonoids in cantaloupes, leading to an increased accumulation of secondary metabolites. Additionally, it also improves the postharvest storage quality of cantaloupes.

Exogenous proline suppresses endogenous proline and proline-production genes but improves the salinity tolerance capacity of salt-sensitive rice by stimulating antioxidant mechanisms and photosynthesis.

Salinity is a critical environmental stress factor that significantly reduces crop productivity and yield. A mutant B-type response regulator gene (hst1) has been shown to promote salinity tolerance in the YNU genotype. Previous studies on the hst1 gene showed a higher proline production capacity under salt stress. Using almost identical genetic backgrounded salt-tolerant (YNU) and salt-sensitive (Sister line) rice genotypes, we tested the function of proline in the hst1 gene salinity-tolerance mechanism by applying exogenous proline under control and salt-stress conditions. Morpho-physiological, biochemical, and molecular analysis of ST and SS plants was performed to clarify the salinity tolerance mechanism mediated by the exogenous proline. The ST and SS genotypes accumulated exogenous proline, and the ST genotype has higher proline levels than the SS genotype. However, exogenous proline improved salt tolerance only in the SS genotype. Exogenous proline promotes plant and root growth by stimulating photosynthetic pigments and photosynthesis. The exogenous proline has a reductive effect on MDA, and H2O2 protects plants against ROS. Interestingly, exogenous proline lowers Na+ and raises K+ accumulations under salt stress. In the SS genotype, exogenous proline increases the activity of antioxidant enzymes (SOD, CAT, and APX) to protect against salinity-induced damage. The exogenous proline application down-regulates proline-synthesis genes (OsP5CS1 and OsP5CR) and up-regulates proline-degradation genes. Also, exogenous proline increases the expression of the OsSalT and OsGRAS29 genes, improving salinity tolerance in the SS genotype. Our study has demonstrated that proline plays a significant role in conferring salt tolerance with the salinity-tolerance-related hst1 mechanisms.

Identification of new targets for glioblastoma therapy based on a DNA expression microarray.

This study provides a comprehensive perspective on the deregulated pathways and impaired biological functions prevalent in human glioblastoma (GBM). In order to characterize differences in gene expression between individuals diagnosed with GBM and healthy brain tissue, we have designed and manufactured a specific, custom DNA microarray. The results obtained from differential gene expression analysis were validated by RT-qPCR. The datasets obtained from the analysis of common differential expressed genes in our cohort of patients were used to generate protein-protein interaction networks of functionally enriched genes and their biological functions. This network analysis, let us to identify 16 genes that exhibited either up-regulation (CDK4, MYC, FOXM1, FN1, E2F7, HDAC1, TNC, LAMC1, EIF4EBP1 and ITGB3) or down-regulation (PRKACB, MEF2C, CAMK2B, MAPK3, MAP2K1 and PENK) in all GBM patients. Further investigation of these genes and enriched pathways uncovered in this investigation promises to serve as a foundational step in advancing our comprehension of the molecular mechanisms underpinning GBM pathogenesis. Consequently, the present work emphasizes the critical role that the unveiled molecular pathways likely play in shaping innovative therapeutic approaches for GBM management. We finally proposed in this study a list of compounds that target hub of GBM-related genes, some of which are already in clinical use, underscoring the potential of those genes as targets for GBM treatment.

Exploring a Desirable Quadr-mRNAs Panel for Non-invasive and Ultrasensitive Bladder Cancer Diagnosis: In-silico and Clinical Studies.

BACKGROUND: Most patients with non-muscle invasive bladder cancer (NMIBC) have a high direction for recurrence and disease progression, which remains a significant unresolved challenge in bladder cancer patients. Therefore, a constant search is necessary for identifying appropriate and reliable biomarkers for early diagnosis of NMIBC. The current study has aimed to search for valuable diagnostic biomarkers in the tissue and urine specimens of NMIBC patients. METHODS: The changes of twelve candidate mRNAs in a screening phase (40 tissue samples of NMIBC patients and their corresponding 40 urine specimens) and a subsequent independent validation phase (40 urine specimens) were estimated using real-time polymerase chain reaction (RT-qPCR). The receiver operating characteristic (ROC) analysis was executed to determine the potential diagnostic values of mRNAs. RESULTS: The mRNA levels of seven candidate genes were markedly higher in tissue specimens relative to their neighboring tissues. Among them, four mRNAs, including ERBB2, CCND1, MKI67, and MAGEA6, were differentially expressed in urine samples of NMIBC patients relative to control subjects. Further, the expression of these four mRNAs was validated in the validation step. Combining these biomarkers showed better diagnostic performance than single biomarkers in the urine sample for non-invasive NMIBC detection. The combination of these mRNAs and cytology enhanced the sensitivity of cytology from 37% to 87%. CONCLUSION: Our findings suggested that a four-mRNA panel may be promising in the non-invasive diagnosis of NMIBC, which deserves further investigation.