Protein-protein Interaction Analysis Research Articles

Unveiling the interplay of YAP1-driven pathways and miR-340-5P expression: insights into nasopharyngeal cancer metastasis.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China, with a notable incidence in Indonesia. This study aimed to characterize the expression and correlation of Yes-associated protein (YAP1) and miR-340-5p in NPC metastasis tissues. This study utilized clinical samples from primary tumors of NPC patients to investigate the expression of YAP1 and miR-340-5p. The Cancer Genome Atlas (TCGA) Head and Neck Cancer dataset was analyzed to assess YAP1 and miR-340-5p expression in broader head and neck cancer samples. Protein-protein interaction (PPI) and functional enrichment analyses were performed to understand the putative regulatory mechanisms of YAP1 and miR-340-5p head and neck cancer. YAP1 mRNA and miR-340-5p level expression were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and statistical analyses were performed to compare the expression of these markers in NPC samples. Analysis of clinical samples revealed lower expression levels of YAP1 and miR-340-5p in metastasis NPC cases compared to non-metastatic cases (p<0.0001). YAP1 and miR-340-5p revealed a negative correlation in metastasis and non-metastasis samples but were statistically insignificant. Additionally, both genes showed significantly lower expression in stage IVB compared to stage II, III, and IVA NPC tissues (p<0.0001). The TCGA dataset showed consistent decreases in YAP1 and miR-340-5p expression in head and neck cancer tumors as opposed to normal tissues. Functional enrichment and PPI analysis suggested the involvement of the Hippo signaling pathway and other cancer-related pathways in NPC progression. The study highlights the under-expressed YAP1 and miR-340-5p in metastasis tumor cases, suggesting their potential role as a tumor suppressor in NPC.

Comparative transcriptomic analysis reveals osmoregulatory mechanisms of juvenile Lateolabrax maculatus responses to long term hypotonic and hypertonic acclimation

Salinity limits the abundance and distribution of some fishes in a particular ecological niche. The spotted sea bass (Lateolabrax maculatus), an euryhaline species, exhibits remarkable adaptability to various salinity levels. To elucidate the osmoregulation mechanisms of this species, the growth performance, serum biochemical parameters and gill transcriptomic profiles of the juvenile spotted sea bass subjected to long term hypotonic (0 ppt) and hypertonic environment (30 and 45 ppt), with the isotonic environment (12 ppt) as the control, were investigated. During the 30 days' salinity acclimation, the growth performance of the juvenile sea bass was inhibited significantly (P < 0.05) at hypertonic condition of 45 ppt, while no significant differences were observed among those at 0, 12, and 30 ppt. The serum biochemical indicators of plasma osmolality, concentration of Na+, Cl−, glucose, urea, total protein, and ALT and AST activities significantly increased during the hypertonic acclimation. Transcriptome analysis identified 1179, 103, and 443 differentially expressed genes in the 0, 30, and 45 ppt salinity groups, respectively, compared to the isotonic (12 ppt) group. Bioinformatics analysis revealed that signal transduction pathways were promoted during hypotonic acclimation, while energy metabolism pathways were activated during hypertonic acclimation. Protein-protein interaction and WGCNA analysis identified hub genes that may play important functions during acclimation. Among them, protein synthesis related-genes including Rps15, Rps16, Rps9, Rpl4, Rpl15, Rpl30, Rpl31, Rpl13a and Eef2 were down-regulated under hypotonic acclimation, metabolic related-genes including Cs, Idh2, Idh3, Mdh2, Pck1, Pck2, Pdha1 and Ldhb were up-regulated under the hypertonic condition. Rac1 were up-regulated in both conditions. This study provides new insights into the osmoregulatory mechanisms of spotted sea bass in response to long-term hypotonic and hypertonic acclimation.

VOLATILE ANTIDIABETIC PROPERTIES OF PIPER NIGRUM L. ETHANOL EXTRACT (ORIGINAL AND PLANT STEM CELL): NETWORK PHARMACOLOGY STUDY AND ANTIOXIDANT ACTIVITY

Objective: This study aims to identify and compare the active chemical components in the ethanol extracts of Piper nigrum L. (black pepper) plant and its callus and to investigate their potential roles in treating diabetes mellitus through Protein-Protein Interaction (PPI) analysis. Methods: Ethanol extracts were prepared from both the original black pepper plant and its callus. Chemical analysis identified key active substances, including piperine and β-D-Glucopyranoside, using Retention Times (RT). PPI investigations were conducted to determine the interactions involved in diabetes management. The antioxidant capacities of the extracts were assessed using IC50 values, and the biological processes and molecular functions related to diabetes treatment were evaluated. Results: Both the original plant and callus extracts contained active substances such as piperine (37.715%, RT: 28.1967) and β-D-Glucopyranoside (54.272%, RT: 16.5768). The primary biological processes identified were the P450 epoxygenase pathway and glycogen production. Additionally, the organic acid metabolic process and nucleosome core were implicated in the management of diabetes mellitus by the extracts. The main molecular functions predicted were p53 binding and cyclin. The antioxidant capacities of the extracts were moderate for the callus extract (IC50: 129.92±0.83) and poor for the original plant extract (IC50: 156.69±1.36). Conclusion: The study reveals that the ethanol extracts from the black pepper callus and the original plant possess distinct chemical profiles and mechanisms in treating diabetes mellitus. The callus extract demonstrates a more favorable antioxidant capacity compared to the original plant extract. Both extracts engage in similar biological processes but exhibit differences in their chemical composition and potential therapeutic pathways for diabetes management.

Mechanistic study of Nidus Vespae inhibiting gastric cancer in vitro through the JAK2/STAT3 signaling pathway

Ethnopharmacological relevanceNidus Vespae, an animal-derived traditional Chinese medicine, has a long-standing history in treating inflammatory conditions and tumor-related diseases. Notably, Nidus Vespae decoction (NVD) has been shown to inhibit the proliferation of gastric cancer cells, although the underlying mechanisms remain unclear. ObjectiveThis study aimed to elucidate the efficacy and mechanisms by which NVD exerts its therapeutic effects on gastric cancer. Materials and methodsWe employed the Cell Counting Kit-8 (CCK-8) assay to assess the impact of NVD on gastric cancer cell proliferation, while flow cytometry was utilized to evaluate cell cycle arrest and apoptosis. Differentially expressed proteins (DEPs) were identified by proteomics analysis, which were further analyzed through Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Protein-protein interaction (PPI) analysis was conducted to identify the hub genes. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted to assess mRNA and protein levels related to apoptosis, cell cycle regulation, and the JAK2/STAT3 pathway. Rescue experiments with Colivelin TFA confirmed the role of NVD in inhibiting gastric cancer cell proliferation. UPLC-HRMS and HS-SPME-GC-MS technologies were performed to analyze the composition of NVD, and the bioinformatics tool called BATMAN-TCM database was used for functional analyses. ResultsOur results demonstrated that NVD significantly hindered the proliferation of gastric cancer cells, initiated programmed cell death, and induced cell cycle arrest in G2/M or G0/G1 phases in various gastric carcinoma cells in vitro. The identified DEPs were involved in several cancer-related pathways and signal transduction processes, notably the JAK-STAT receptor signaling pathway. NVD was found to down-regulate the JAK2/STAT3 signaling cascade, and reactivation of STAT3 diminished its anti-gastric cancer effects. Finally, the ingredient-target-disease network analysis also verified the anti-tumor effect of NVD. ConclusionThis study highlights the potential of Nidus Vespae as a therapeutic agent for gastric cancer, providing insights into its molecular mechanisms of action.

Exploration and identification of diabetes targets in nursing: CDH1 and DVL1.

Diabetes is a chronic disease caused by absolute or relative insufficiency of insulin secretion and impaired insulin utilization. CDH1 and DVL1 role in diabetes and its nursing care is unclear. The diabetes dataset GSE21321 and GSE19790 profiles were downloaded from the gene expression omnibus (GEO) database. Perform differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network construction and analysis, functional enrichment analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and Comparative Toxicogenomics Database (CTD) analysis. Gene expression heat map was drawn. TargetScan was used to screen the miRNA that regulates central DEGs. 1983 DEGs were obtained. According to Gene Ontology (GO) analysis, they were mainly enriched in signal regulation, catenin complexes, and signal receptor binding. In Kyoto Encyclopedia of Gene and Genome (KEGG) analysis, they were mainly concentrated in the Rap1 signaling pathway, cAMP signaling pathway, and Hippo signaling pathway. The DEGs are mainly enriched in cell signaling, Wnt signaling vesicles, growth factor activity, and the interaction between neural active ligands and receptors. In the enrichment project of Metascape, BMP signaling pathways and cell population proliferation can be seen in the GO enrichment project. The soft threshold power in WGCNA is set to 5. A total of 15 modules were generated. Core gene expression heatmap showed that core genes (CTNNB1, CDH1, DVL1) were highly expressed in diabetes samples. CTD analysis showed thatCTNNB1, CDH1, DVL1were associated with weight gain, inflammation, and necrosis. CDH1 and DVL1 are highly expressed in diabetes and may become molecular targets for diabetes and its care.

In silico genome-wide analysis of the growth-regulating factor gene family and their expression profiling in Vitis vinifera under biotic stress.

Growth regulatory factors (GRFs) are transcription factors that encode the proteins involved in plant growth and development. However, no comprehensive analysis of Vitis vinifera GRF genes has yet been conducted. In the current study, we performed a genome-wide analysis of the GRF gene family to explore the VvGRF gene's role in Vitis vinifera. We identified 30 VvGRF genes in the Vitis vinifera genome, localized over 20 chromosomes. Based on evolutionary analysis, 49 GRF genes (nine AtGRF, ten FvGRF, and 30 VvGRF) were clustered into six groups. Many cis-elements involved in light control, defense, and plant growth have been identified in the promoter region of VvGRF genes, and multiple miRNAs have been predicted to be involved in regulating VvGRF gene expression. Protein-protein interaction analysis showed that nine VvGRF proteins formed a complex protein interaction network. Furthermore, the gene expression analysis of VvGRF revealed that VvGRF-5 and VvGRF-6 were highly upregulated suggesting that these genes are involved in biotic responses. This study provides comprehensive insights into the functional characteristics and occurrence of the VvGRF gene family in Vitis vinifera, which may be applied in breeding programs to enhance the growth of Vitis vinifera varieties under stress and growth changes.

Proteome-wide Mendelian randomization and functional studies uncover therapeutic targets for polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is an endocrine syndrome that affects a large portion of women worldwide. This proteogenomic and functional study aimed to uncover candidate therapeutic targets for PCOS. We comprehensively investigated the causal association between circulating proteins and PCOS using two-sample Mendelian randomization analysis. Cis-protein quantitative trait loci were derived from six genome-wide association studies (GWASs) on plasma proteome. Genetic associations with PCOS were obtained from a large-scale GWAS meta-analysis, FinnGen cohort, and UK Biobank. Colocalization analyses were performed to prioritize the causal role of candidate proteins. Protein-protein interaction (PPI) and druggability evaluation assessed the druggability of candidate proteins. We evaluated the enrichment of tier 1 and 2 candidate proteins in individuals with PCOS and a mouse model and explored the potential application of the identified drug target. Genetically predicted levels of 65 proteins exhibited associations with PCOS risk, with 30 proteins showing elevated levels and 35 proteins showing decreased levels linked to higher susceptibility. PPI analyses revealed that FSHB, POSTN, CCN2, and CXCL11 interacted with targets of current PCOS medications. Eighty medications targeting 20 proteins showed their potential for repurposing as therapeutic targets for PCOS. EGLN1 levels were elevated in granulosa cells and the plasma of individuals with PCOS and in the plasma and ovaries of dehydroepiandrosterone (DHEA)-induced PCOS mouse model. As an EGLN1 inhibitor, administration of roxadustat in the PCOS mouse model elucidated the EGLN1-HIF1α-ferroptosis axis in inducing PCOS and validated its therapeutic effect in PCOS. Our study identifies candidate proteins causally associated with PCOS risk and suggests that targeting EGLN1 provides a promising treatment strategy.

Causal relationship between hypothyroidism and ulcerative colitis: a bidirectional Mendelian randomization study.

Ulcerative colitis (UC) and Hashimoto's thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran's Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36-69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells.

YTHDC1 Regulates the Migration, Invasion, Proliferation, and Apoptosis of Rheumatoid Fibroblast-Like Synoviocytes.

Rheumatoid arthritis (RA), a chronic autoimmune condition, is characterized by persistent synovial inflammation, bone degradation, and progressive joint deterioration. Despite considerable research efforts, the precise molecular mechanism underlying RA remains elusive. This investigation aims to elucidate the potential role and molecular mechanism of N6-methyladenosine (m6A) methylation regulators in the pathogenesis of RA. In this study, we employed bioinformatics tools to elucidate the association between RA and m6A modifications, aiming to identify potential biological markers. We extracted datasets GSE12021, GSE55235, and GSE55457 from the Gene Expression Omnibus (GEO) database for comprehensive analysis. Utilizing differential expression analysis, protein-protein interaction (PPI) analysis, and single-cell sequencing techniques, we identified pivotal hub genes implicated in the pathogenesis of RA. Subsequently, we assessed the correlation between these hub genes and the pathogenesis of RA using Gene Set Enrichment Analysis (GSEA). Both in vivo and in vitro experiments were performed to confirm the expression and functional roles of the identified key hub gene in RA. Differential expression analysis, PPI analysis, and single-cell analysis identified three key hub genes (YTHDC1, YTHDC2, and YTHDF2) associated with RA. GSEA results further revealed that these genes are enriched in pathways associated with inflammatory responses. Subsequent correlation analysis demonstrated a significant negative correlation between YTHDC1 expression and CD8+ T cell levels. Notably, the gene and protein expression levels of YTHDC1 and YTHDF2 were significantly reduced in the synovial tissue of RA patients. Furthermore, silencing YTHDC1 in fibroblast-like synoviocytes (FLSs) significantly inhibited their migration, invasion, proliferation, and induced apoptosis. YTHDC1 may potentially be involved in the pathogenesis of RA through its regulation of migration, invasion, proliferation, and apoptosis in FLSs.

Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression.

Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue.

Comprehensive bioinformatic analysis identified m6A methylation as an important regulator in mediating immune response during idiopathic pulmonary arterial hypertension

Abstract Background Despite its functional importance in various fundamental bioprocesses, studies of N6-methyladenosine (m6A) in the pulmonary arterial hypertension (PAH) are lacking. Here we studied the potential relevance of m6A RNA methylation and immune response in PAH development. Methods We constructed a monocrotaline (MCT) induced PAH rat model and performed Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). The 18 idiopathic PAH (IPAH) microarray data obtained from the GEO database was used to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). CIBERSORT was used to investigate the effect of m6A methylation on immune cell infiltration during PAH. Results A differential pattern of m6A abundance, mainly up-methylation, was observed in the lung tissues of rats with MCT induced PAH. By WGCNA, multi-list pathway enrichment analysis and protein-protein interaction (PPI) analysis, we found that m6A methylation modification may play important roles in mediating immune response during PAH. CYBERSORT algorithm indicated that the m6A methylation can drive monocyte to form M1 macrophage, which may be mediated by CCR5 and CXCL9. Conclusion Collectively, m6A landscape is altered in PAH. We summarize newly discovered m6A in controlling immune response, which caused activation of M1 macrophage during PAH. It’s provided a novel insight into the therapeutic mechanisms of PAH.

Transcriptomic analysis of the gonads of Locusta migratoria (Orthoptera: Acrididae) following infection with Paranosema locustae.

Paranosema locustae is an environmentally friendly parasitic predator with promising applications in locust control. In this study, transcriptome sequencing was conducted on gonadal tissues of Locusta migratoria males and females infected and uninfected with P. locustae at different developmental stages. A total of 18,635 differentially expressed genes (DEGs) were identified in female ovary tissue transcriptomes, with the highest number of DEGs observed at 1 day post-eclosion (7141). In male testis tissue transcriptomes, a total of 32,954 DEGs were identified, with the highest number observed at 9 days post-eclosion (11,245). Venn analysis revealed 25 common DEGs among female groups and 205 common DEGs among male groups. Gene ontology and Kyoto Encyclopaedia of Genes and Genome analyses indicated that DEGs were mainly enriched in basic metabolism such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, and immune response processes. Protein-protein interaction analysis results indicated that L. migratoria regulates the expression of immune- and reproductive-related genes to meet the body's demands in different developmental stages after P. locustae infection. Immune- and reproductive-related genes in L. migratoria gonadal tissue were screened based on database annotation information and relevant literature. Genes such as Tsf, Hex1, Apolp-III, Serpin, Defense, Hsp70, Hsp90, JHBP, JHE, JHEH1, JHAMT, and VgR play important roles in the balance between immune response and reproduction in gonadal tissues. For transcriptome validation, Tsf, Hex1, and ApoLp-III were selected and verified by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation analysis revealed that the qRT-PCR expression patterns were consistent with the RNA-Seq results. These findings contribute to further understanding the interaction mechanisms between locusts and P. locustae.

Multiple Omics Analyses Reveal Activation of Nitrogen Metabolism and Flavonoid Glycosylation in Toxicodendron vernicifluum Under High Temperature.

Lacquer trees (Toxicodendron vernicifluum), economically vital, face high-temperature stress in summer. Transcriptomic, proteomic, and metabolomic analyses were employed to investigate the mechanisms by which lacquer trees respond to high temperatures. High-temperature treatment led to notable metabolite changes with 224 upregulated and 69 downregulated. Indole-3-acetic acid remained stable while abscisic acid decreased, with increases in jasmonic acid and jasmonoyl-L-isoleucine indicating complex hormonal responses. JAR1 and ABA 8'-hydroxylase encoding genes were upregulated. The rise in JAs boosted the alkaloid content and activated nitrogen transport. High temperatures also increased specific amino acids and upregulated aminotransferase and protease-encoding genes. Metabolomic analysis showed elevated flavonoid glycosides and the upregulation of glycosyltransferase genes. WPCNA found 35 protein modules involved in secondary metabolite biosynthesis, protein phosphorylation, and signal transduction. Protein-protein interaction analysis revealed MYC6's link with flavonoid biosynthesis, indicating its role in promoting flavonoids.

Exploring the Regulatory Interaction of Differentially Expressed Proteins in Cleft Palate Induced by Retinoic Acid.

This study aimed to identify novel proteins involved in retinoic acid (RA)-induced embryonic cleft palate development. The palate tissues of the control and RA-treated E14.5 were dissected and subjected to iTRAQ-based proteomic analysis. Differential expression analysis identified 196 significantly upregulated and 149 downregulated considerably proteins in RA-induced palate tissues. Comprehensive Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed the significant involvement of cytoplasmic translation, ribosome biogenesis, glycolysis/gluconeogenesis, and glutathione metabolism pathways in cleft palate pathogenesis triggered by RA. In particular, ribosome-related pathways were highly enriched, while glycolysis was disrupted. Protein-protein interaction analysis, facilitated by the STRING database, revealed a tightly interconnected network of differentially expressed proteins. Further analysis using the cytoHubba plugin in Cytoscape identified ten hub proteins, including Eif4a1, Gapdh, Eno1, Imp3, Rps20, Rps27a, Eef2, Hsp90ab1, Rpl19, and Rps16, indicating their potential roles in RA-induced cleft palate development, and thus positioning them as potential biomarkers for cleft palate. These findings provide valuable insights into the proteomic changes associated with RA-induced cleft palate and shed light on key pathways and proteins that can contribute significantly to the pathogenesis of this congenital condition.

Mechanism of Gastrodin against neurotoxicity based on network pharmacology, molecular docking and experimental verification

BackgroundDisorders of glutamate metabolism and excessive release participat in multiple neuronal pathologies including ischemic stroke (IS), Alzheimer's disease (AD), or Parkinson's disease (PD). Recently, herbal medicines have been widely used and have shown satisfactory results in the treatment of neurological disorders. Gastrodin is a traditional Chinese medicine (TCM) used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. This research examines the neuroprotective effects of Gastrodin against glutamate-induced neurotoxicity in neuronal cells. MethodsThe HERB database was used to explore the active ingredients and target genes of Gastrodia Elata. The STRING database and Cytoscape software were used to screen and construct the Protein-Protein Interaction (PPI). Furthermore, we used molecular docking to predict the potential targets of Gastrodin. The effects of Gastrodin were revealed by western blot, calcium imaging, membrane clamp, CCK8 and flow cytometry. Neuronal oxidative stress and damage were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Neuronal morphology was examined using Golgi-Cox staining. Finally, animal behavior was examined using novel object recognition and fear conditioning tests. ResultsWe have obtained 22 components such as TM10, TM17, TM25 (Gastrodin), and 281 targets such as AKT, EGFR, and CDK1 through network pharmacology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed these genes were significantly enriched in protein phosphorylation, protein serine/threonine/tyrosine kinase activity, apoptosis and HIF-1 signaling pathways, etc. A higher affinity between Gastrodin and AKT was revealed by PPI analysis and molecular docking. Further, Gastrodin significantly inhibited Ca2+ influxes and excitatory synaptic transmission in cortical neurons. In addition, Gastrodin effectively alleviated neuron apoptosis, oxidative stress and damage. ConclusionGastrodin has neuroprotective effects against glutamate-induced neurotoxicity.

Therapeutic mechanism and key active ingredients of Yinxing Mihuan Oral Solution in coronary heart disease comorbidity with anxiety: A network pharmacology and molecular docking approach.

Yinxing Mihuan Oral Solution (YMOS) is a Chinese patent medicine for treating coronary heart disease combined anxiety (CHDCA), but the molecular mechanism of its treatment is still unclear. This article aims to understand the molecular mechanism, optimize clinical drug use, and guide new drug development. Using the Swiss Target Prediction database, we obtained the main chemical composition of YMOS. Then we used network pharmacology to identify their potential targets. Network construction, coupled with protein-protein interaction and enrichment analysis was used to identify representative components and core targets. Finally, molecular docking simulation was conducted to further refine the drug-target interaction. Forty-two active chemicals were found in YMOS and 91 target genes related to CHDCA. The treatment effect was found to be associated with 1908 biological processes and 160 pathways, as revealed by the outcomes of the enrichment analysis. The potential therapeutic mechanisms of the drug are closely related to its antioxidant, anti-inflammatory, and vascular function regulation pathways, and the main core targets include albumin, tumor necrosis factor, TP53, AKT serine/threonine kinase 1, interleukin 1 beta, and vascular endothelial growth factor A. The potential molecular mechanisms of YMOS in CHDCA treatment were identified using network pharmacology and molecular docking approaches. The results reveal the systemic biological implications of YMOS. This study has systematically uncovered the molecular mechanism of YMOS for the first time, offering fresh insights for evidence-based clinical applications.

Decoding Critical Targets and Signaling Pathways in EBV-Mediated Diseases Using Large Language Models.

Epstein-Barr virus (EBV), a member of the gamma herpesvirus, is the first identified human oncovirus and is associated with various malignancies. Understanding the intricate interactions between EBV antigens and cellular pathways is crucial to unraveling the molecular mechanisms in EBV-mediated diseases. However, fully elucidating EBV-host interactions and the associated pathogenesis remains a significant challenge. In this study, we employed large language models (LLMs) to screen 36,105 EBV-relevant scientific publications and summarize the current literature landscape on various EBV-associated diseases like Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), nasopharyngeal carcinoma (NPC), and so on. LLM-generated data indicate that the most-studied EBV-associated pathways are enriched in immune response, apoptosis, cell growth, and replication. The analyses of protein-protein interactions (PPIs) reveal three principal EBV-related protein clusters: TP53-centered apoptotic factors, EBV-associated transcription factors, and immune response elements. Utilizing our dataset and public databases, we demonstrated that BLLF3-targeted TLR2-associated factors are effective diagnostic markers for DLBCL. Next, we confirmed the co-expression of LMP1-targeted calcium pathway factors in BL. Finally, we demonstrated the correlation and co-expression of LMP1-induced PARP1, HIF1A, HK2, and key glycolysis-related factors, further suggesting that LMP1 actively regulates the glycolysis pathway. Therefore, our study presents a comprehensive functional encyclopedia of the interactions between EBV antigens and host signaling pathways across various EBV-associated diseases, providing valuable insights for the development of therapeutic strategies.

The m6A and immune regulatory gene signature predicts the prognosis and correlates with immune infiltration of head and neck squamous cell carcinoma

Recent investigations have underscored the epigenetic modulation of the immune response; however, the interplay between RNA N6-methyladenosine (m6A) modification and immunomodulation in head and neck squamous cell carcinoma (HNSC) remains relatively unexplored. To bridge this knowledge gap, we undertook an extensive examination of the potential contributions of m6A modification and immunomodulation in HNSC. We amalgamated and deduplicated 27 m6A -related genes (m6AGs) and 1342 immune regulation-related genes (IMRGs), resulting in a comprehensive dataset encompassing 1358 genes. This dataset was scrutinized for m6A modification and immunomodulatory patterns within HNSC specimens. Employing Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) technique, we developed a prognostic risk model for m6A regulator-mediated methylation modification and immunomodulation-related differentially expressed genes (m6A&IMRDEGs). Our differential expression analysis delineated 29 m6A&IMRDEGs, and Weighted Gene Co-expression Network Analysis (WGCNA) elucidated two module genes (IL11 and MMP13) subjected to correlation analysis. The prognostic prediction models revealed that the clinical predictive efficacy peaked for 1-year forecasts, followed sequentially by 3-year and 5-year predictions. The risk scores derived from the model adeptly categorized HNSC patients into high- and low-risk cohorts, with the high-risk group exhibiting a more unfavorable prognosis. Protein-Protein Interaction (PPI) analysis identified 7 hub genes implicated in m6A and immune regulation, namely BPIFB1, BPIFB2, GP2, MUC5B, MUC7, PIP, and SCGB3A1. Furthermore, we noted marked disparities in the expression profiles of 18 immune cell types between the high- and low-risk groups. Our results substantiate that the clustering subpopulations and risk models associated with m6A and immune regulatory genes portend a poor prognosis in HNSC. The risk score emerges as a potent prognostic biomarker and predictive metric for HNSC patients. A thorough assessment of m6A and immune regulatory genes in HNSC will augment our comprehension of the tumor immune microenvironment and facilitate the advancement of HNSC therapeutics.

Increasing nitrogen use efficiency in agronomically important plants: An insight into gene characteristics on a genome-wide scale in barley

Nitrogen (N) is a critical element for plant growth and development. Hence, improving nitrogen use efficiency (NUE) is vital for reducing costs and the environmental impact of agricultural practices. Understanding the genetic control of N metabolism is crucial to improve NUE, especially in agronomically important plants, such as barley (Hordeum vulgare).Using bioinformatics and functional genomics tools, we identified and characterized sixteen barley nitrogen metabolism-related gene families (HvNMGs) on a genome-wide scale, analysing gene features and evolution. These genes, located on six of seven barley chromosomes, are highly conserved in plants (including barley, rice, and Arabidopsis), as shown by phylogenetic analysis. We further explored the evolutionary relationships of NMGs through a genome-to-genome synteny analysis, which indicated higher conservation of NMGs between barley and other monocots, suggesting that these orthologous pairs predate species divergence. Protein-protein interaction analyses revealed that all of the HvNMGs show interactions, mainly with each other. The H. vulgare miRNAs target sites (hvu-miR) prediction identified six hvu-miR in 4 HvNMGs (HvGABA-T2, HvALDH10-1, HvALDH10-2 and HvARGAH), indicating their potential involvement in stress responses. The expression patterns analysis of publicly available RNA-seq data revealed that HvNMGs are expressed in all developmental stages of barley, and they respond to different stress conditions, indicating their essential role in plant growth, development and stress response. The organ-specific expression analysis, conducted using qPCR, of HvNMGs revealed higher expression of HvNiR and HvNRs in the leaf and significantly higher expression of HvARGAH and HvALDH10 in the spike than in other tissues, showing that some of the genes may be particularly important in some tissues than others. This data provides a foundation for understanding HvNMG function and could be used to improve barley yield by enhancing NUE — an important goal for both crop productivity and environmental sustainability.

RNA-seq analysis of mitochondria-related genes regulated by AMPK in the human trophoblast cell line BeWo.

How AMP activated protein kinase (AMPK) signaling regulates mitochondrial functions and mitophagy in human trophoblast cells remains unclear. This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq. We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2 (PRKAA1/2) knockdown (AKD) and control BeWo cells using the Seahorse real-time ATP rate test, then analyzed gene expression profiling by RNA-seq. Differentially expressed genes (DEG) were examined by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then protein-protein interactions (PPI) among mitochondria related genes were further analyzed using Metascape and Ingenuity Pathway Analysis (IPA) software. Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells (CT), with a greater reduction of mitochondrial ATP production. A total of 1092 DEGs were identified, with 405 upregulated and 687 downregulated. GO analysis identified 60 genes associated with the term 'mitochondrion' in the cellular component domain. PPI analysis identified three clusters of mitochondria related genes, including aldo-keto reductase family 1 member B10 and B15 (AKR1B10, AKR1B15), alanyl-tRNA synthetase 1 (AARS1), mitochondrial ribosomal protein S6 (MRPS6), mitochondrial calcium uniporter dominant negative subunit beta (MCUB) and dihydrolipoamide branched chain transacylase E2 (DBT). In summary, this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells, and among them, three clusters of genes may potentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.