Integrative biology : quantitative biosciences from nano to macro最新文献

{"title":"The diagnosis and prognostic value and biological function of annexin A2 in hepatocellular carcinoma: a bioinformatic and experimental study.","authors":"Ya Li, Huhu Zhang, Fulin Sun, Chunjuan Yu, Shuyao Jiang, Lina Yang","doi":"10.1093/intbio/zyaf017","DOIUrl":"10.1093/intbio/zyaf017","url":null,"abstract":"<p><p>Annexin A2 (ANXA2) is a Annexin family proteins member that plays a role in regulating cell growth and signal transduction pathways. However, its role in hepatocellular carcinoma (HCC) remains incompletely elucidated. We used bioinformatics methods to analyze the expression, diagnosis and prognostic value of ANXA2 in HCC using data from the TCGA, GTEx, GEO, HCCDB, HPA databases. Next, we predicted ANXA2-associated proteins and constructed a protein-protein interaction network via the STRING database. Furthermore, we obtained the biological processes associated with ANXA2 in HCC through GO, KEGG and GSEA enrichment analysis. Finally, CCK8, wound healing, and transwell were used to verify these biological processes in HCCLM3 cell lines. Insight box ANXA2 is highly expressed in a variety of tumors, with significantly higher levels in HCC than in normal tissues. ANXA2 expression is positively correlated with T stage, histologic grade, residual tumor, pathologic stage, tumor status and fibrosis ishak score in HCC, and high ANXA2 expression suggests a poorer prognosis. Additionally, ANXA2 has diagnostic value in HCC. Its expression is closely associated with S100A family proteins and immune infiltration. Enrichment analysis showed that high ANXA2 expression activates biological processes such as epithelial-mesenchymal transition (EMT), NF-κB and Wnt signaling pathways. The results of cell experiment were consistent with bioinformatics analysis. Our study explored the role of ANXA2 in the occurrence and development of HCC, which may provide reference for the treatment of HCC.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LARP4B inhibits ferroptosis and accelerates the progression of pancreatic cancer by activating WNK1-induced NRF2/GCH1/BH4 pathway.","authors":"Jiehao Tu, Lun Zhang","doi":"10.1093/intbio/zyaf019","DOIUrl":"10.1093/intbio/zyaf019","url":null,"abstract":"<p><p>Ferroptosis plays a crucial role in inhibiting tumor progression. La Ribonucleoprotein 4B (LARP4B) is known to function as a pro-oncogenic factor in digestive tumors, but its specific role and potential mechanisms remain unclear in pancreatic cancer (PC). In this study, we found that LARP4B was upregulated in PC tissues and cells. Overexpression of LARP4B promoted PC cell proliferation and invasion, while knockdown of LARP4B inhibited PC cell proliferation and invasion. Furthermore, knockdown of LARP4B was associated with intracellular iron overload, increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and decreased glutathione (GSH) content and superoxide dismutase (SOD) activity in PC cells. Mechanistically, LARP4B binds to mRNA of with-no-lysine kinase 1 (WNK1) and promotes its stability, and WNK1 competitively binds to the partial Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to promote the nuclear translocation of nuclear factor erythroid-2-related factor 2 (NRF2), thereby activating the NRF2/GCH1/BH4 pathway and inhibiting ferroptosis in PC cells. ML385, a NRF2 nuclear translocation inhibitor, partially rescued the inhibitory effect of WNK1 on ferroptosis in PC cells. Finally, in vivo experiments showed that knockdown of LARP4B suppressed tumor growth in PC xenograft mice. In conclusion, our study demonstrated that LARP4B inhibited ferroptosis by activating the WNK1-mediated NRF2/GCH1/BH4 pathway, thereby promoting PC progression. Insight Box This work provides evidence for LARP4B as a pro-oncogenic factor in pancreatic cancer, while also offers new insights into the further understanding of the biological functions of LARP4B and the oncological mechanisms of pancreatic cancer. We found that LARP4B is upregulated in PC tissues and cells, and its overexpression promotes the proliferation and invasion of PC cells. Additionally, we discovered that LARP4B binds to WNK1 mRNA and enhances its stability. WNK1 competitively binds to Keap1 to facilitate NRF2 nuclear translocation, thereby activating the NRF2/GCH1/BH4 pathway and inhibiting ferroptosis in PC cells. These findings provide significant insights for further research on PC and the development of therapeutic strategies.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of protein-protein interaction sites between Russell's viper PLA2 and the γ-phospholipase inhibitor PIP from the amino acid frequency distribution of a bio-panned peptide set.","authors":"Karthika Rajan, Margaret Reick, Aswathy Alangode, Martin Reick","doi":"10.1093/intbio/zyaf012","DOIUrl":"10.1093/intbio/zyaf012","url":null,"abstract":"<p><p>We screened a random peptide phage display library using Russell's viper venom phospholipase A2 (RV-PLA2) as bait. Sequence information from the resulting set of bio-panned heptapeptides was analyzed and mined to determine likely sites of interaction between two subunits of RV-PLA2 homo dimers and between RV-PLA2 and the γPLA2 inhibitor PIP from Malayopython reticulatus. This was accomplished in part by sequence alignment of the affinity-selected peptides with the sequences of RV-PLA2 and PIP. Because similarity scores calculated from sequence alignments proved inadequate to determine interaction interfaces accurately for RV-PLA2 dimers, we explored the use of amino acid frequency-based interactions scores (SFI/SFIN) for a more accurate prediction of protein-protein interaction sites. Heptamers with elevated SFI(N) scores were compared to interfaces of interaction observed in crystal structures of RV-PLA2 homodimers and to sites of interaction predicted by protein-protein docking between structures of RV-PLA2 and model of PIP. Segments with a high density of protein-protein contacts coincided with heptamer sequences exhibiting SFI and/or SFIN scores significantly above average, in both RV-PLA2 homodimers and in RV-PLA2 γPLI heteromeric structures. Elevated SFI and SFIN scores were associated with peptide function since the heptamers with some of the highest SFI and SFI(N) scores, LPGLPLS, GLPLSLQ and SLQNGLY constitute the known PLA2 inhibitor P-PB.I (LPGLPLSLQNGLY) while KLGRVDI, and WDGVYIR, constitute PIP-17 (LGRVDIHVWDGVYIRGR), IC50 for hsPLA2: 5.3 μM. A graph showing the alignment of maxima between SFI scores and average solvent accessibility (per heptamer) suggests that solvent accessibility is a major driver of both protein-protein interaction and phage selection. Insights We show by computational methods that in sets of small phage-displayed peptides of the same length selected for binding to the same target protein, amino acids contributing to binding at a particular position occur at higher frequencies than in random peptides. This position-specific selection of particular amino acids can be detected in the position-specific amino acid frequency distribution of that set of selected peptides. Therefore, when this position-specific amino acid frequency is mapped back onto a particular amino acid sequence of the same length, the sum of these frequencies can function as a measure of enrichment of selected amino acids.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identify new pseudogene RPL7P1-oriented network as a drug target against infections pre-existing diabetes.","authors":"Jiajun Chen, Chenxi Li, Ying Wang, Shiwei Chen, Xiangqi Li","doi":"10.1093/intbio/zyaf015","DOIUrl":"10.1093/intbio/zyaf015","url":null,"abstract":"<p><strong>Background: </strong>Diabetes coexisting with infections (DCI) significantly increases the risk of severe outcomes and mortality in patients. This study proposes that RPL7P1, an uncharacterized pseudogene, plays a role in the pathogenesis of DCI.</p><p><strong>Methods: </strong>Using a multifaceted approach, we employed experimental datasets from ENCODE to identify key genes. Drug repositioning was performed using gene network analysis with z-scores and the ROCR package. Network expansion was facilitated by NetworkAnalyst's core algorithms, with disease validation through the NHGRI GWAS Catalog. Cytoscape was utilized for network visualization.</p><p><strong>Results: </strong>Our findings reveal RPL7P1's potential involvement in DCI through modulation of CBL and STXBP3 by sequestering hsa-miR-144-3p, interaction with IGF2BP2 protein, and crosstalk with ATP6V1E1 RNA. Single-cell profiling pinpointed endothelial cells as a potential signaling nexus. Therapeutic agents targeting the RPL7P1-centric network showed promise in managing infections in diabetic patients. Additionally, we identified key molecular players, the m6A modification of RPL7P1, and its role in cuproptosis-a novel form of cell death.</p><p><strong>Conclusion: </strong>This research elucidates the potential role of the novel pseudogene RPL7P1 in DCI, highlighting the importance of pseudogenes in complex diseases and providing novel insights into the epigenetic modulation of diabetes complicated by infections. Insight Box Diabetes and infections often coexist, complicating our understanding of their shared mechanisms. To address this, we employed a comprehensive suite of bioinformatics methods, including pathway mapping, ceRNA analysis, PPI evaluation, single-cell dissection, network modeling, and drug repositioning strategies. Our research revealed that RPL7P1 modulates signaling pathways by sponging miR-144-3p, interacting with IGF2BP2 and ATP6V1E1 RNA, and influencing cuproptosis-a novel form of cell death-through m6A modification, a key RNA modification. We identified endothelial cells as key mediators of the RPL7P1 network in the liver. Additionally, our integrative approach uncovered five potential therapeutic drugs targeting the RPL7P1 network. These findings provide novel insights into coexisting diabetes and infections, underscoring the value of multidisciplinary strategies in uncovering coexisting disease mechanisms and treatment opportunities.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP46 sensitizes BeWo trophoblasts to ferroptosis by stabilizing CIRBP.","authors":"Linlin Hu, Caihong Chen","doi":"10.1093/intbio/zyaf010","DOIUrl":"10.1093/intbio/zyaf010","url":null,"abstract":"<p><p>Preeclampsia is a type of pregnancy complication that manifests as hypertension and albuminuria, associated with improper development of blood vessels in the placenta. However, the precise cause of preeclampsia is not well defined. Ferroptosis is a type of cell death involving abnormal accumulation of iron and lipid reactive oxygen species (ROS) in cells. Accumulating evidence indicates that ferroptosis may contribute to preeclampsia development, but the underlying mechanism remains unclear. Several ubiquitin-specific proteases (USPs) have been reported to repress ferroptosis, but whether other USPs regulate ferroptosis and preeclampsia development remains elusive. Here we identified USP46 as a potent regulator of erastin-induced ferroptosis in BeWo trophoblasts, which serve as an in vitro model to study preeclampsia. We found that overexpression of USP46 promoted erastin-induced ferroptosis in BeWo cells, while knockdown of USP46 led to resistance to erastin-induced ferroptosis. This resistance could be reversed by excessive cold-inducible RNA-binding protein (CIRBP). Immunoprecipitation experiments showed that USP46 interacts with CIRBP to inhibit its ubiquitination. These findings suggest that USP46 sensitizes BeWo cells to ferroptosis by stabilizing CIRBP. Insight Box Preeclampsia is a severe pregnancy complication with an unknown pathogenesis. Studies have shown that several ubiquitin-specific proteases (USPs) can inhibit ferroptosis and affect the occurrence of preeclampsia. However, given the numerous genes in the USP family, it remains unclear whether other USPs regulate ferroptosis and the development of preeclampsia. In this study, we identified USP46 as a strong regulator of ferroptosis in BeWo cells. USP46 interacts with CIRBP to reduce its ubiquitination and stabilize its expression, thereby promoting ferroptosis. This study reveals the key role of USP46 in regulating ferroptosis and provides a new target for etiological research and treatment of preeclampsia.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explicating miRNA-mediated regulation of inflammatory pathways in COPD, MS, and lung cancer using explainable artificial intelligence: insights from peripheral blood profiles.","authors":"Nakul Tanwar, Yasha Hasija","doi":"10.1093/intbio/zyaf020","DOIUrl":"10.1093/intbio/zyaf020","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD), multiple sclerosis (MS), and lung cancer are linked by shared inflammatory pathways and immune dysregulation. miRNAs regulate these processes by influencing gene expression, yet their roles in the molecular mechanisms across neurological and respiratory systems are not fully understood.</p><p><strong>Objective: </strong>This study aims to identify miRNAs and their target genes regulating inflammatory pathways, advancing the understanding of molecular genetics underlying COPD, MS, and lung cancer.</p><p><strong>Methods: </strong>miRNA expression data (GSE61741) were analyzed using a Random Forest (RF) model optimized via Grid Search and validated with Stratified K-Fold cross-validation. Synthetic Minority Oversampling (SMOTE) addressed data imbalance, while SHapley Additive exPlanations (SHAP) identified key miRNAs. Functional enrichment and pathway analyses explored miRNA-gene interactions. Single-cell level analysis further validated the cell-specific roles of these genes. An independent dataset (GSE31568) was used for validation.</p><p><strong>Results: </strong>Key miRNAs, including hsa-let-7c, hsa-miR-454, hsa-miR-92a, and hsa-miR-223, were identified as regulators of hallmark inflammatory genes such as CCL2, IL6, ITGB3, and MYC. These genes are critical for cytokine signaling, epithelial repair, and immune modulation. Single-cell analysis highlighted the role of inflammatory fibroblasts in localized inflammation and tissue remodeling. The RF model achieved an accuracy of 81.58%, validated at 82.55%. Pathway analysis emphasized cytokine-cytokine receptor interactions and shared pathways between neurological and respiratory diseases.</p><p><strong>Conclusions: </strong>This study identifies miRNAs and their target genes as critical regulators of inflammation in COPD, MS, and lung cancer. Single-cell insights and pathway enrichment provide a comprehensive view of shared molecular mechanisms, contributing to biomarker discovery and therapeutic strategies for precision medicine in inflammatory diseases.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145351348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The creation and validation of a fully animal component-free media for select adherent cell types.","authors":"Nicolette B Mogilever, Marie-Hélène Godin Pagé, Anjolaoluwatikiitan Solola, Andrew E Pelling","doi":"10.1093/intbio/zyaf009","DOIUrl":"10.1093/intbio/zyaf009","url":null,"abstract":"<p><p>Fetal Bovine Serum (FBS) is one of the most commonly used media supplement for the maintenance of mammalian cell types, yet the expensive costs, ethical concerns, and lot-to-lot variation have provoked a clear need for a serum that is standardized and derived from non-animal sources. Several serum-free formulations have been developed in the past, however they are often cell type specific, contain animal-derived components, and lack long-term culture validation. In this study, we developed a novel animal component-free (ACF) media and investigated its effectiveness on four commonly used mammalian cell lines via long-term (up to 90 days) morphological, transcriptomic, and proliferative analyses. Cells cultured in our ACF medium exhibited comparable cellular morphologies and equal or greater growth rates compared with cells cultured with FBS. Additionally, differentially expressed genes between the FBS-grown and ACF-grown groups were predominantly associated with functions linked to proliferation and cell attachment. While the tested cells were initially derived using conventional methods and include non-human lines, this study demonstrates that our medium supports long-term culture without animal-derived supplements. The findings from this study indicate that this medium is a suitable replacement to FBS-containing medium for several common cell lines. Insight Box Traditional cell culture methods often rely on animal-derived components, which can pose ethical and economic challenges. The use of animal serum in vitro is needed to supply nutrients to cells but raises concerns about animal welfare and introduces variability and contaminants that can negatively affect downstream applications. This study presents a novel animal component-free medium designed to support the growth of adherent cell types, providing a sustainable alternative to serum. Here, we demonstrate long-term cell viability, normal morphology, and differential gene expression patterns indicative of enhanced proliferation and attachment in cells cultured in 2D environments. By addressing the demand for ethical and reproducible cell culture methods, this research aims to contributes to the broader adoption of sustainable practices in biotechnology.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KCTD10 promoting PD-L1 expression in colorectal cancer enhanced the anti-tumor effect of PD-1 antibody.","authors":"Zihao Yin, Rongyu Su, Shengwen Long, Guo Chen, Shuanglin Xiang","doi":"10.1093/intbio/zyaf014","DOIUrl":"10.1093/intbio/zyaf014","url":null,"abstract":"<p><p>Colorectal cancer is a highly prevalent malignant tumor of the digestive tract worldwide. Immunotherapy has emerged as a critical therapeutic approach for CRC patients. We observed that KCTD10 expression is significantly downregulated in colorectal cancer tissues compared to normal tissues, and patients with higher KCTD10 expression exhibited prolonged survival. To investigate its functional role, we established stable KCTD10-overexpressing CT26 and SW480 colorectal cancer cell lines. Both in vitro and in vivo experiments demonstrated that KCTD10 overexpression suppresses colorectal cancer progression and inhibits the EMT process. Notably, KCTD10 overexpression upregulated PD-L1 expression and synergistically enhanced the therapeutic efficacy of anti-PD-1 treatment. Our findings reveal that KCTD10 functions as a tumor suppressor in colorectal cancer pathogenesis. Mechanistically, KCTD10 potentiates the antitumor efficacy of anti-PD-1 immunotherapy by upregulating PD-L1 expression, thereby proposing a novel therapeutic target and suggesting a promising combination strategy for CRC treatment. Insight box KCTD10 can inhibit the development of colorectal cancer and the EMT process. And the over-expression of KCTD10 increased the expression of PD-L1, improved the efficacy of PD-1 treatment.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative bioinformatics and drug repurposing for metastatic prostate cancer: identifying novel therapeutic targets by transcriptional profiling and molecular Modeling.","authors":"Haseeb Nisar, Jignesh Prajapati, Asma Muhammad Mumtaz, Atiqa Iftikhar, Faria Faran, Rimsha Hamid Mehmood, Samiah Shahid, Dweipayan Goswami","doi":"10.1093/intbio/zyaf016","DOIUrl":"10.1093/intbio/zyaf016","url":null,"abstract":"<p><p>Metastasis is one of the leading factors of cancer-related deaths worldwide. New potential targets and treatment strategies are needed to extend survival and enhance the quality of life for these patients. We performed an in-depth bioinformatics analysis to identify potential genes and associated potential therapeutic compounds for metastasis of prostate adenocarcinoma. The differentially expressed genes (DEGs) were first identified using four datasets (GSE8511), (GSE3325), (GSE27616) and (GSE6919) present in the Gene Expression Omnibus (GEO) database and analyzed using the GEO2R. WGCNA was performed to find a significant gene cluster. Network analysis was performed using MCODE and Cytohubba plugins of Cytoscape to select hub genes. Moreover, expression validation of key genes was carried out using the TCGA dataset. Functional annotation and pathway enrichment analyses were conducted for validation, while survival analysis was applied to assess potential therapeutic effects. DEGs retrieved from the GEO were submitted to the Connectivity Map database to identify potentially related compounds. Molecular docking, ADMET analysis and drug-likeness properties, MD simulations and MM-GBSA analysis were performed to screen for the best potential drugs. We identified three compounds-Prunetin, Ofloxacin, and ALW-II-49-7 that may help extend disease-free survival in patients with tumor metastasis. Additionally, ACTA2, MYLK, and CNN1 were recognized as potential therapeutic targets for these compounds. These drugs' potential effectiveness and binding efficiency were screened using induced fit molecular docking followed by 100 ns MD-based Simulations and MM-GBSA analysis. However, further in vitro and in vivo studies are needed to confirm these findings. Insight box This study integrates microarray gene expression profiling with bioinformatics tools to identify differentially expressed genes (DEGs) and co-expression networks using WGCNA. Network analysis in Cytoscape was used to screen hub genes, and the Connectivity Map (cMAP) database was searched for potential candidate drugs. Binding efficiency of repurposed drugs was evaluated using molecular docking, molecular dynamics (MD) simulations, and MM-GBSA analysis. Our findings provide the potential therapeutic drugs and targets of prostate adenocarcinoma metastasis with possibilities for follow-up in vitro and in vivo validation.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":"17 ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144986405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution and emergence: higher order information structure in protein interactomes across the tree of life.","authors":"Brennan Klein,&nbsp;Erik Hoel,&nbsp;Anshuman Swain,&nbsp;Ross Griebenow,&nbsp;Michael Levin","doi":"10.1093/intbio/zyab020","DOIUrl":"https://doi.org/10.1093/intbio/zyab020","url":null,"abstract":"<p><p>The internal workings of biological systems are notoriously difficult to understand. Due to the prevalence of noise and degeneracy in evolved systems, in many cases the workings of everything from gene regulatory networks to protein-protein interactome networks remain black boxes. One consequence of this black-box nature is that it is unclear at which scale to analyze biological systems to best understand their function. We analyzed the protein interactomes of over 1800 species, containing in total 8 782 166 protein-protein interactions, at different scales. We show the emergence of higher order 'macroscales' in these interactomes and that these biological macroscales are associated with lower noise and degeneracy and therefore lower uncertainty. Moreover, the nodes in the interactomes that make up the macroscale are more resilient compared with nodes that do not participate in the macroscale. These effects are more pronounced in interactomes of eukaryota, as compared with prokaryota; these results hold even after sensitivity tests where we recalculate the emergent macroscales under network simulations where we add different edge weights to the interactomes. This points to plausible evolutionary adaptation for macroscales: biological networks evolve informative macroscales to gain benefits of both being uncertain at lower scales to boost their resilience, and also being 'certain' at higher scales to increase their effectiveness at information transmission. Our work explains some of the difficulty in understanding the workings of biological networks, since they are often most informative at a hidden higher scale, and demonstrates the tools to make these informative higher scales explicit.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"283-294"},"PeriodicalIF":2.5,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39745285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}