Delirium is a prevalent cognitive disorder among older patients and a common phenomenon following major surgical procedures. This study aimed to identify the significant proteomic biomarkers and examine their association with postoperative delirium (POD). Four electronic databases were used to identify the published articles between 1st January 2000 and 31st December 2023. Among the included 40 studies, the meta-analysis investigated 13 potential cytokines and inflammatory biomarker proteins linked with postoperative delirium. The Hedge’s g standardized mean difference (SMD) was applied to calculate the effect size, with 95% confidence intervals (CIs), under the fixed effect or random effect model based on the heterogeneity index of I². Patients with POD exhibited significantly higher elevated levels of inflammatory biomarkers IL-6 (SMD = 1.45), CRP (SMD = 1.26), GFAP (SMD = 1.15), IL-1B (SMD = 0.95), IL-10 (SMD = 0.57), IL-8 (SMD = 0.56), MCP-1 (SMD = 0.39), and NFL (SMD = 0.44), suggesting that these proteins may play an inevitable role in delirium-associated cytokines and inflammatory response, development and progression of delirium. Conversely, a reduction in IGF-1 protein level (SMD = − 0.24) was also significantly associated with POD, suggesting a potential vulnerability to delirium. This study paves the way for future research aimed at early diagnosis, personalized treatment, and the development of novel therapeutic strategies to manage delirium effectively.

Delirium and Alzheimer's disease (AD) are common causes of cognitive dysfunction among older adults. These neurodegenerative diseases share a common and complex relationship, and can occur individually or concurrently, increasing the chance of permanent mental dysfunction. However, the common molecular pathophysiology, key proteomic biomarkers, and functional pathways are largely unknown, whereby delirium is superimposed on AD and dementia. We employed an integrated bioinformatics and system biology analysis approach to decipher such common key proteomic signatures, pathophysiological links between delirium and AD by analyzing the gene expression data of AD-affected human brain samples and comparing them with delirium-associated proteins. The present study identified the common drug target hub-proteins examining the protein–protein interaction (PPI) and gene regulatory network analysis. The functional enrichment and pathway analysis was conducted to reveal the common pathophysiological relationship. Finally, the molecular docking and dynamic simulation was used to computationally identify and validate the potential drug target and repurposable drugs for delirium and AD. We detected 99 shared differentially expressed genes (sDEGs) associated with AD and delirium. The sDEGs-set enrichment analysis detected the transmission across chemical synapses, neurodegeneration pathways, neuroinflammation and glutamatergic signaling pathway, oxidative stress, and BDNF signaling pathway as the most significant signaling pathways shared by delirium and AD. The disease-sDEGs interaction analysis highlighted the other disease risk factors with delirium and AD development and progression. Among the sDEGs of delirium and AD, the top 10 hub-proteins including ALB, APP, BDNF, CREB1, DLG4, GAD1, GAD2, GFAP, GRIN2B and GRIN2A were found by the PPI network analysis. Based on the maximum molecular docking binding affinities and molecular dynamic simulation (100 ns) results, the ALB and GAD2 were found as prominent drug target proteins when tacrine and donepezil were identified as potential drug candidates for delirium and AD. The study outlined the common key biomolecules and biological pathways shared by delirium and AD. The computationally reported potential drug molecules need a deeper investigation including clinical trials to validate their effectiveness. The outcomes from this study will help to understand the typical pathophysiological relationship between delirium and AD and flag future therapeutic development research for delirium.

Non-small-cell lung cancer (NSCLC) is considered as one of the malignant cancers that causes premature death. The present study aimed to identify a few potential novel genes highlighting their functions, pathways, and regulators for diagnosis, prognosis, and therapies of NSCLC by using the integrated bioinformatics approaches. At first, we picked out 1943 DEGs between NSCLC and control samples by using the statistical LIMMA approach. Then we selected 11 DEGs (CDK1, EGFR, FYN, UBC, MYC, CCNB1, FOS, RHOB, CDC6, CDC20, and CHEK1) as the hub-DEGs (potential key genes) by the protein–protein interaction network analysis of DEGs. The DEGs and hub-DEGs regulatory network analysis commonly revealed four transcription factors (FOXC1, GATA2, YY1, and NFIC) and five miRNAs (miR-335-5p, miR-26b-5p, miR-92a-3p, miR-155-5p, and miR-16-5p) as the key transcriptional and post-transcriptional regulators of DEGs as well as hub-DEGs. We also disclosed the pathogenetic processes of NSCLC by investigating the biological processes, molecular function, cellular components, and KEGG pathways of DEGs. The multivariate survival probability curves based on the expression of hub-DEGs in the SurvExpress web-tool and database showed the significant differences between the low- and high-risk groups, which indicates strong prognostic power of hub-DEGs. Then, we explored top-ranked 5-hub-DEGs-guided repurposable drugs based on the Connectivity Map (CMap) database. Out of the selected drugs, we validated six FDA-approved launched drugs (Dinaciclib, Afatinib, Icotinib, Bosutinib, Dasatinib, and TWS-119) by molecular docking interaction analysis with the respective target proteins for the treatment against NSCLC. The detected therapeutic targets and repurposable drugs require further attention by experimental studies to establish them as potential biomarkers for precision medicine in NSCLC treatment.

Background: Delirium is a prevalent neuropsychiatric medical phenomenon that causes serious emergency outcomes, including mortality and morbidity. It also increases the suffering and the economic burden for families and carers. Unfortunately, the pathophysiology of delirium is still unknown, which is a major obstacle to therapeutic development. The modern network-based system biology and multi-omics analysis approach has been widely used to recover the key drug target biomolecules and signaling pathways associated with disease pathophysiology. This study aimed to identify the major drug target hub-proteins associated with delirium, their regulatory molecules with functional pathways, and repurposable drug candidates for delirium treatment. Methods: We used a comprehensive proteomic seed dataset derived from a systematic literature review and the Comparative Toxicogenomics Database (CTD). An integrated multi-omics network-based bioinformatics approach was utilized in this study. The STRING database was used to construct the protein-protein interaction (PPI) network. The gene set enrichment and signaling pathways analysis, the regulatory transcription factors and microRNAs were conducted using delirium-associated genes. Finally, hub-proteins associated repurposable drugs were retrieved from CMap database. Results: We have distinguished 11 drug targeted hub-proteins (MAPK1, MAPK3, TP53, JUN, STAT3, SRC, RELA, AKT1, MAPK14, HSP90AA1 and DLG4), 5 transcription factors (FOXC1, GATA2, YY1, TFAP2A and SREBF1) and 6 microRNA (miR-375, miR-17-5, miR-17-5p, miR-106a-5p, miR-125b-5p, and miR-125a-5p) associated with delirium. The functional enrichment and pathway analysis revealed the cytokines, inflammation, postoperative pain, oxidative stress-associated pathways, developmental biology, shigellosis and cellular senescence which are closely connected with delirium development and the hallmarks of aging. The hub-proteins associated computationally identified repurposable drugs were retrieved from database. The predicted drug molecules including aspirin, irbesartan, ephedrine-(racemic), nedocromil, and guanidine were characterized as anti-inflammatory, stimulating the central nervous system, neuroprotective medication based on the existing literatures. The drug molecules may play an important role for therapeutic development against delirium if they are investigated more extensively through clinical trials and various wet lab experiments. Conclusion: This study could possibly help future research on investigating the delirium-associated therapeutic target biomarker hub-proteins and repurposed drug compounds. These results will also aid understanding of the molecular mechanisms that underlie the pathophysiology of delirium onset and molecular function.

Dicer‐like (DCL), Argonaute (AGO), and RNA‐dependent RNA polymerase (RDR) are known as the three major gene families that act as the critical components of RNA interference or silencing mechanisms through the noncoding small RNA molecules (miRNA and siRNA) to regulate the expressions of protein‐coding genes in eukaryotic organisms. However, most of their characteristics including structures, chromosomal location, subcellular locations, regulatory elements, and gene networking were not rigorously studied. Our analysis identified 7 TaDCL, 39 TaAGO, and 16 TaRDR genes as RNA interference (RNAi) genes from the wheat genome. Phylogenetic analysis of predicted RNAi proteins with the RNAi proteins of Arabidopsis and rice showed that the predicted proteins of TaDCL, TaAGO, and TaRDR groups are clustered into four, eight, and four subgroups, respectively. Domain, 3D protein structure, motif, and exon‐intron structure analyses showed that these proteins conserve identical characteristics within groups and maintain differences between groups. The nonsynonymous/synonymous mutation ratio (Ka/Ks) < 1 suggested that these protein sequences conserve some purifying functions. RNAi genes networking with TFs revealed that ERF, MIKC‐MADS, C2H2, BBR‐BPC, MYB, and Dof are the key transcriptional regulators of the predicted RNAi‐related genes. The cis‐regulatory element (CREs) analysis detected some important CREs of RNAi genes that are significantly associated with light, stress, and hormone responses. Expression analysis based on an online database exhibited that almost all of the predicted RNAi genes are expressed in different tissues and organs. A case‐control study from the gene expression level showed that some RNAi genes significantly responded to the drought and heat stresses. Overall results would therefore provide an excellent basis for in‐depth molecular investigation of these genes and their regulatory elements for wheat crop improvement against different stressors.

Background: Despite the development of advanced cancer therapies, achieving cancer eradication remains challenging. Radioimmunotherapy (RIT) is an innovative approach that combines radionuclides with monoclonal antibodies targeting tumour-associated antigens or those expressed by the tumour microenvironment. Over the past two decades, RIT has been extensively researched, along with two RIT products—⁹⁰Y-ibritumomab tiuxetan and ¹³¹I-tositumomab. However, despite its demonstrated efficacy in non-solid tumours, RIT’s clinical use remains limited, and its effectiveness in solid tumours is inconclusive. This study aimed to analyse randomised controlled trials (RCTs) to evaluate the overall clinical effectiveness of RIT across different cancer types and its impact on treatment outcomes. Methods: A systematic search of PubMed, EMBASE, Scopus, CENTRAL, and Google Scholar was conducted from January 2000 to October 2024 in accordance with PRISMA guidelines and the PICOS framework. Studies were included if they were RCTs evaluating RIT for cancer treatment and reported treatment outcomes such as overall survival (OS), progression-free survival (PFS), disease-free survival, or time to progression (TTP). Data extraction was performed using a standardised Excel form, and study quality was assessed with the Joanna Briggs Institute Critical Appraisal Tool for RCTs. A narrative synthesis of the data was complemented by meta-analyses where feasible, particularly for progression- and survival-related endpoints. Results: Out of 2241 records identified, 20 RCTs encompassing approximately 3562 patients were included. The majority of trials focused on non-solid tumours, particularly non-Hodgkin’s lymphoma (NHL), while a smaller subset evaluated solid tumours such as lung, pancreatic, ovarian, and prostate cancers. Most non-solid tumour studies employed ⁹⁰Y-ibritumomab tiuxetan or ¹³¹I-tositumomab, targeting the CD20 antigen, whereas limited evidence exists for RIT efficacy in solid tumours. Meta-analysis of progression-related outcomes yielded a pooled hazard ratio (HR) of 0.48 (95% CI: 0.39–0.59), indicating a 52% reduction in the risk of progression. In contrast, overall survival outcomes were more variable, with a pooled OS HR of 0.80 (95% CI: 0.60–1.07). Adverse events, predominantly haematological and nonhaematological toxicities, were common yet generally reversible. The findings suggest that RIT, especially when used as part of combination regimens, significantly improves treatment outcomes in non-solid tumours but has an inconsistent effect in solid tumour settings. Conclusions: The results underscore the clinical promise of RIT in treating non-solid tumours like NHL, where combination regimens yield superior outcomes compared to monotherapy. However, the inconclusive evidence in solid tumours highlights the need for further large-scale, well-designed RCTs to define the optimal use, dosing, and patient selection for RIT in these settings. Additionally, standardisation in outcome reporting and longer follow-up periods are essential for more accurate economic and clinical assessments. Overall, RIT represents a valuable therapeutic modality, yet its integration into cancer treatment regimens should be guided by further research aimed at mitigating toxicity and optimising combination strategies.