Applied Biochemistry and Biotechnology, Год журнала: 2023, Номер 196(4), С. 2122 - 2136
Опубликована: Июль 20, 2023
Язык: Английский
Scientific Reports, Год журнала: 2025, Номер 15(1)
Опубликована: Март 2, 2025
Type 2 diabetes (T2D) is a crucial risk factor for both pancreatic cancer (PC) and kidney (KC). However, effective common drugs treating PC and/or KC patients who are also suffering from T2D currently lacking, despite the probability of their co-occurrence. Taking disease-specific multiple during co-existence diseases may lead to adverse side effects or toxicity due drug-drug interactions. This study aimed identify T2D-, KC-causing genomic biomarkers (cGBs) highlighting pathogenetic mechanisms explore as treatment. We analyzed transcriptomic profile datasets, applying weighted gene co-expression network analysis (WGCNA) protein-protein interaction (PPI) approaches PC-, cGBs. then disclosed through ontology (GO) terms, KEGG pathways, regulatory networks, DNA methylation these Initially, we identified 78 differentially expressed genes (cDEGs) that could distinguish T2D, PC, samples controls based on profiles. From these, six top-ranked cDEGs (TOP2A, BIRC5, RRM2, ALB, MUC1, E2F7) were selected cGBs considered targets exploring drug molecules each three diseases. Functional enrichment analyses, including GO analyses involving transcription factors (TFs) microRNAs, along with immune infiltration studies, revealed critical molecular linked KC, T2D. Finally, (NVP.BHG712, Irinotecan, Olaparib, Imatinib, RG-4733, Linsitinib) potential treatments co-existence, supported by literature reviews. Thus, this bioinformatics provides valuable insights resources developing genome-guided treatment strategy
Язык: Английский
Процитировано
0
Phytomedicine, Год журнала: 2024, Номер 130, С. 155734 - 155734
Опубликована: Май 12, 2024
Язык: Английский
Процитировано
4
Cell Biology and Toxicology, Год журнала: 2025, Номер 41(1)
Опубликована: Янв. 14, 2025
Thyroid cancer (THCA) is an increasingly common malignant tumor of the endocrine system, with its incidence rising steadily in recent years. For patients who experience recurrence or metastasis, treatment options are relatively limited, and prognosis poor. Therefore, exploring new therapeutic strategies has become particularly urgent. This study confirmed that effective suppression THCA cell proliferation stimulation apoptosis can be achieved through application Ginsenosides-Rh2. Through network pharmacology screening, molecular target Ginsenosides-Rh2 was identified as CHEK1, inhibitory effect by downregulating CHEK1 protein expression. Furthermore, demonstrations conducted both vitro vivo showcased delivering using nanoparticle carriers significantly reduced viability approximately 50%, regulated DNA damage levels, apoptosis-related expression, cycle control. The IC50 formulation determined (B-CPAP = 88.24 μM), TPC 79.52 μM). Cu2O@G-Rh2 suppressing tumors exhibits a significant on metastasis while maintaining good safety. nanoparticles possess excellent stability anti-tumor efficacy. research offers perspectives for demonstrates potential clinical applications.
Язык: Английский
Процитировано
0
BMC Geriatrics, Год журнала: 2024, Номер 24(1)
Опубликована: Авг. 29, 2024
Delirium and Alzheimer's disease (AD) are common causes of cognitive dysfunction among older adults. These neurodegenerative diseases share a complex relationship, can occur individually or concurrently, increasing the chance permanent mental dysfunction. However, molecular pathophysiology, key proteomic biomarkers, functional pathways largely unknown, whereby delirium is superimposed on AD dementia.
Язык: Английский
Процитировано
3
PLoS ONE, Год журнала: 2024, Номер 19(9), С. e0310843 - e0310843
Опубликована: Сен. 30, 2024
Clear cell renal carcinoma (ccRCC) is the most prevalent subtype of kidney cancer. Although there increasing evidence linking ccRCC to genetic alterations, exact molecular mechanism behind this relationship not yet completely known researchers. Though drug therapies are best choice after metastasis, unfortunately, majority patients progressively develop resistance against therapeutic drugs receiving it for almost 2 years. In case, multi-targeted different variants essential effective treatment ccRCC. To understand mechanisms development and progression, explore drugs, identify ccRCC-causing key genes (KGs). order obtain KGs, at first, we detected 133 common differentially expressed (cDEGs) between control samples based on nine (9) microarray gene-expression datasets with NCBI accession IDs GSE16441, GSE53757, GSE66270, GSE66272, GSE16449, GSE76351, GSE66271, GSE71963, GSE36895. Then, filtered these cDEGs through survival analysis independent TCGA GTEx database obtained 54 scDEGs having significant prognostic power. Next, used protein-protein interaction (PPI) network reduced set top-ranked eight KGs ( PLG , ENO2 ALDOB UMOD ALDH6A1 SLC12A3 SLC12A1 SERPINA5 ). The pan-cancer showed association subtypes cancers including gene regulatory (GRN) revealed some crucial transcriptional post-transcriptional regulators KGs. scDEGs-set enrichment significantly identified functions, biological processes, cellular components, pathways that linked results DNA methylation study indicated hypomethylation hyper-methylation which may lead immune infiltrating types (CD8+ T CD4+ cell, B neutrophil, dendritic macrophage) their in ccRCC, where positively correlated cells, but negatively other supported by literature review also. Then 10 repurposable molecules (Irinotecan, Imatinib, Telaglenastat, Olaparib, RG-4733, Sorafenib, Sitravatinib, Cabozantinib, Abemaciclib, Dovitinib.) docking KGs-mediated receptor proteins. Their ADME/T cross-validation receptors, also potent Therefore, outputs might be useful inputs/resources wet-lab researchers clinicians considering an strategy
Язык: Английский
Процитировано
2
Medicina, Год журнала: 2023, Номер 59(10), С. 1705 - 1705
Опубликована: Сен. 24, 2023
Background and Objectives: Breast cancer (BC) is one of the major causes cancer-related death in women globally. Proper identification BC-causing hub genes (HubGs) for prognosis, diagnosis, therapies at an earlier stage may reduce such rates. However, most previous studies detected HubGs through non-robust statistical approaches that are sensitive to outlying observations. Therefore, main objectives this study were explore potential from robustness viewpoints, highlighting their early prognostic, diagnostic, therapeutic performance. Materials Methods: Integrated robust statistics bioinformatics methods databases used obtain required results. Results: We robustly identified 46 common differentially expressed (cDEGs) between BC control samples three microarrays (GSE26910, GSE42568, GSE65194) scRNA-seq (GSE235168) dataset. Then, we eight cDEGs (COL11A1, COL10A1, CD36, ACACB, CD24, PLK1, UBE2C, PDK4) as by protein-protein interaction (PPI) network analysis cDEGs. The performance survival probability prediction models with expressions two independent datasets (GSE45827 GSE54002) TCGA (The Cancer Genome Atlas) database showed our proposed might be considered diagnostic prognostic biomarkers, where genes, COL11A1 exhibit better expression Box plots different stages progression indicated diagnosis prognosis ability. set enrichment GO (Gene ontology) terms KEGG (Kyoto Encyclopedia Genes Genomes) pathways disclosed some biological processes, molecular functions, pathways. Finally, suggested top-ranked six drug molecules (Suramin, Rifaximin, Telmisartan, Tukysa Tucatinib, Lynparza Olaparib, TG.02) treatment docking HubGs-mediated receptors. Molecular results also these inhibit post-translational modification (PTM) sites (Succinylation, phosphorylation, ubiquitination) proteins. Conclusions: This study's findings valuable resources BC.
Язык: Английский
Процитировано
5
BMC Geriatrics, Год журнала: 2023, Номер 23(1)
Опубликована: Ноя. 22, 2023
Abstract Background Delirium is a prevalent neuropsychiatric medical phenomenon that causes serious emergency outcomes, including mortality and morbidity. It also increases the suffering economic burden for families carers. Unfortunately, pathophysiology of delirium still unknown, which major obstacle to therapeutic development. The modern network-based system biology multi-omics analysis approach has been widely used recover key drug target biomolecules signaling pathways associated with disease pathophysiology. This study aimed identify hub-proteins delirium, their regulatory molecules functional pathways, repurposable candidates treatment. Methods We comprehensive proteomic seed dataset derived from systematic literature review Comparative Toxicogenomics Database (CTD). An integrated bioinformatics was utilized in this study. STRING database construct protein-protein interaction (PPI) network. gene set enrichment analysis, transcription factors microRNAs were conducted using delirium-associated genes. Finally, drugs retrieved CMap database. Results have distinguished 11 targeted (MAPK1, MAPK3, TP53, JUN, STAT3, SRC, RELA, AKT1, MAPK14, HSP90AA1 DLG4), 5 (FOXC1, GATA2, YY1, TFAP2A SREBF1) 6 microRNA (miR-375, miR-17-5, miR-17-5p, miR-106a-5p, miR-125b-5p, miR-125a-5p) delirium. pathway revealed cytokines, inflammation, postoperative pain, oxidative stress-associated developmental biology, shigellosis cellular senescence are closely connected development hallmarks aging. computationally identified predicted aspirin, irbesartan, ephedrine-(racemic), nedocromil, guanidine characterized as anti-inflammatory, stimulating central nervous system, neuroprotective medication based on existing literatures. may play an important role against if they investigated more extensively through clinical trials various wet lab experiments. Conclusion could possibly help future research investigating biomarker repurposed compounds. These results will aid understanding molecular mechanisms underlie onset function.
Язык: Английский
Процитировано
4
PLoS ONE, Год журнала: 2024, Номер 19(7), С. e0304425 - e0304425
Опубликована: Июль 18, 2024
COVID-19 caused by SARS-CoV-2 is a global health issue. It yet severe risk factor to the patients, who are also suffering from one or more chronic diseases including different lung diseases. In this study, we explored common molecular signatures for which infections and stimulate each other, associated candidate drug molecules. We identified both (Asthma, Tuberculosis, Cystic Fibrosis, Pneumonia, Emphysema, Bronchitis, IPF, ILD, COPD ) causing top-ranked 11 shared genes ( STAT1 , TLR4 CXCL10 CCL2 JUN DDX58 IRF7 ICAM1 MX2 IRF9 ISG15 as hub of differentially expressed (hub-sDEGs). The gene ontology (GO) pathway enrichment analyses hub-sDEGs revealed some crucial pathogenetic processes regulatory network analysis detected 6 TFs proteins micro RNAs key transcriptional post-transcriptional factors hub-sDEGs, respectively. Then proposed guided three repurposable molecules (Entrectinib, Imatinib, Nilotinib), treatment against with This recommendation based on results obtained docking using AutoDock Vina GLIDE module Schrödinger. selected were optimized through density functional theory (DFT) observing their good chemical stability. Finally, binding stability highest-ranked receptor protein RELA top-ordered drugs Nilotinib) 100 ns dynamic (MD) simulations YASARA Desmond Schrödinger observed consistent performance. Therefore, findings study might be useful resources diagnosis therapies patients
Язык: Английский
Процитировано
1
American Journal of Cancer Research, Год журнала: 2024, Номер 14(5), С. 2424 - 2438
Опубликована: Янв. 1, 2024
The inhibitor of DNA-binding 2 (ID2) plays a major role in tumor dedifferentiation non-small cell lung cancer (NSCLC).Studies have indicated an inverse correlation between ID2 expression and NSCLC invasiveness.However, the mechanisms through which activation is regulated are currently unclear.We overexpressed H1299 cells extensively characterized their cellular behaviors.By employing serial deletion approach combined with reporter assay, we pinpointed basal promoter region ID2.We also examined DNA methylation status to elucidate epigenetic driving regulation.Our results revealed that overexpression effectively inhibited migration, invasion, proliferation, colony formation abilities cells.The from -243 +202 played transcriptional activity ID2.Sequence analysis transcription factor Yin Yang 1 (YY1) might be crucial regulation expression.The ectopically expressed YY1 activated both levels promoter, potentially contributing its repressive on growth.Furthermore, site-directed mutagenesis chromatin immunoprecipitation assays may target -120 -76 sites thereby activating activity.The regions were fully methylated CL1-5 cells, level was correlated promoter.Moreover, YY1-induced suppression counteracted by knockdown, suggests represses growth ID2.Our indicate transactivating contribute repression ID2.
Язык: Английский
Процитировано
0
PLoS ONE, Год журнала: 2024, Номер 19(12), С. e0309827 - e0309827
Опубликована: Дек. 19, 2024
Delirium is a severe neuropsychiatric illness that occurs frequently in intensive care and postoperative units which results prolonged hospital stays increases patient’s mortality morbidity rates. This review focused on accumulating the common key proteomic signatures significantly associated with delirium. We carried out systematic literature of studies delirium biomarkers published between 1 st January 2000 31 December 2023 from following electronic bibliographic databases including PubMed, Scopus, EBSCOhost (CINAHL, Medline). A total 1746 were identified reviewed, 78 included our review. The PRISMA guidelines, PEO framework, JBI quality assessment method followed this to maintain inclusion exclusion criteria risk bias assessment. Most cohort (68%) case-control (23%) design. have accumulated 313 proteins or gene encoded 189 unique. Among unique proteins, we top 13 most investigated (IL-6, CRP, IL-8, S100B, IL-10, TNF-a, IL-1b, Cortisol, MCP-1, GFAP, IGF-1, IL-1ra, NFL) are these cytokines inflammatory indicating strong interconnection There was remarkable inconsistency among reporting specific potential biomarker. No single biomarker can be solely used diagnose predict current provides rationale for further molecular investigation delirium-related biomarkers. Also, it’s recommended conduct in-depth research decipher drug target biomolecules prognostic, diagnostic, therapeutic development against
Язык: Английский
Процитировано
0