Mina Amiri, Sevda Jafari, Afsaneh Lavasanifar, Ommoleila Molavi, Soheila Montazersaheb
{"title":"Nano-delivery of Silibinin Potentiate the Induction of Immunogenic Cell Death (ICD) in Melanoma Cells.","authors":"Mina Amiri, Sevda Jafari, Afsaneh Lavasanifar, Ommoleila Molavi, Soheila Montazersaheb","doi":"10.2174/0113892010280336240227062954","DOIUrl":"10.2174/0113892010280336240227062954","url":null,"abstract":"<p><strong>Background: </strong>Induction of immunogenic cell death (ICD) in tumors can enhance antitumor immunity and modulate immunosuppression in the tumor microenvironment (TME).</p><p><strong>Objective: </strong>In the current study, we investigated the effect of silibinin, a natural compound with anticancer activity, and its polymer-based nanoformulations on the induction of apoptosis and ICD in cancer cells.</p><p><strong>Methods: </strong>Free and nanoparticulate silibinin were evaluated for their growth-inhibitory effects using an MTT assay. Annexin V/PI staining was used to analyze apoptosis. Calreticulin (CRT) expression was measured by flow cytometry. Western blotting was conducted to examine the levels of elf2α, which plays a role in the ICD pathway. The HSP90 and ATP levels were determined using specific detection kits.</p><p><strong>Results: </strong>Compared to the free drug, silibinin-loaded nanocarriers significantly increased the induction of apoptosis and ICD in B16F10 cells. ICD induction was characterized by significantly increased levels of ICD biomarkers, including CRT, HSP90, and ATP. We also observed an increased expression of p-elf-2α/ elf-2α in B16F10 cells treated with silibinin-loaded micelles compared to cells that received free silibinin.</p><p><strong>Conclusion: </strong>Our findings showed that the encapsulation of silibinin in polymeric nanocarriers can potentiate the effects of this drug on the induction of apoptosis and ICD in B16F10 melanoma cells.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"392-401"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hsiang-Hung Cheng, Mei Luo, Jing-Rong Jiang, Chun-Xia Wang
{"title":"In Rheumatoid Arthritis, A Review of ncRNAs Related to NF-κB Signaling Pathways.","authors":"Hsiang-Hung Cheng, Mei Luo, Jing-Rong Jiang, Chun-Xia Wang","doi":"10.2174/0113892010262829240214061103","DOIUrl":"10.2174/0113892010262829240214061103","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an autoimmune disease with no known cure that results in joint deformities and dysfunction, significantly impacting the quality of life of patients. The abnormal NF-κB signaling pathway in RA has emerged as a crucial research area for the development of RA therapies, with non-coding RNAs (ncRNAs) serving as a potentially meaningful avenue to regulate it. Thus, understanding the role of ncRNAs in RA and the identification of new therapeutic targets have become pressing issues in the field. In this review, we aim to summarize recent studies on ncRNAs that regulate the NF-κB signaling pathway in RA, including miRNAs, lncRNAs, and circRNAs, as well as the mechanisms by which drugs modulate NF-κB activity. By highlighting these recent advances, we hope to promote further research into targeted RA therapy and provide novel directions and ideas for researchers in the field.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"319-327"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent Advances in Immunotherapy and Targeted Therapy of Triple Negative Breast Cancer.","authors":"Harshada Shewale, Abhishek Kanugo","doi":"10.2174/0113892010303244240718075729","DOIUrl":"10.2174/0113892010303244240718075729","url":null,"abstract":"<p><p>The truancy of representation of the estrogen, progesterone, and human epidermal growth factor receptors occurs during TNBC. TNBC is recognized for the upper reappearance and has a poorer diagnosis compared with rest breast cancer (BC) types. Presently, as such, no targeted therapy is approved for TNBC and treatment options are subjected to chemotherapy and surgery, which have high mortality rates. Hence, the current article focuses on the scenario of TNBC vital pathways and discusses the latest advances in TNBC treatment, including immune checkpoint inhibitors (ICIs), PARP suppressors, and cancer vaccines. Immunotherapy and ICIs, like PD 1 and PD L1 suppressors, displayed potential in clinical trials (CTs). These suppressors obstruct the mechanisms which allow tumor cells to evade the system thereby boosting the body's defense against TNBC. Immunotherapy, either alone or combined with chemotherapy has demonstrated patient outcomes such as increased survival rates and reduced treatment-related side effects. Additionally, targeted therapy approaches include BRCA/2 mutation poly ribose polymerase inhibitors, Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors, Epidermal growth factor receptor inhibitors, Fibroblast growth factor inhibitors, Androgen Receptor inhibitors, PIK3/AKT/mTOR pathway inhibitors, Cyclin-dependent kinase (CDK) inhibitors, Notch signaling pathway inhibitors, Signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors, Chimeric antigen receptor T (CAR-T) cell therapy, Transforming growth factor (TGF) -β inhibitors, Epigenetic modifications (EPM), Aurora Kinase inhibitors and antibody-drug conjugates. We also highlight ongoing clinical trials and potential future directions for TNBC therapy. Despite the challenges in treating TNBC, recent developments in understanding the molecular and immune characteristics of TNBC have opened up new opportunities for targeted therapies, which hold promise for improving outcomes in this aggressive disease.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"365-391"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression and Function of FAM72A Gene in Multiple MyelomaFAM72A.","authors":"Wenyu Gao, Yanping Ma","doi":"10.2174/0113892010311258240729080309","DOIUrl":"10.2174/0113892010311258240729080309","url":null,"abstract":"<p><strong>Aims: </strong>This study aims to comprehensively investigate the role of Family Member A with sequence similarity 72-A (FAM72A) in multiple myeloma.</p><p><strong>Background: </strong>Multiple myeloma poses significant challenges. This study delves into FAM72A's impact on key cellular processes, shedding light on potential therapeutic targets and enhancing our understanding of multiple myeloma progression.</p><p><strong>Objectives: </strong>Investigate the impact of FAM72A on the proliferation, apoptosis, and bortezomib sensitivity of multiple myeloma cell line U266.</p><p><strong>Methods: </strong>qRT-PCR analyzed FAM72A expression levels in bone marrow samples from 30 patients with multiple myeloma and 10 healthy donors at the Second Hospital of Shanxi Medical University. Cell lines overexpressing FAM72A were constructed, and Cell Counting Kit 8 (CCK-8) and flow cytometry were used to assess U266 cell proliferation, apoptosis, and sensitivity to bortezomib. Biological predictions for FAM72A were performed to find transcription factors binding to the FAM72A promoter region, verified using a luciferase assay. U266 cells were transfected with si-POU2F2 (POU class 2 homeobox 2), and the impact on cell proliferation was validated. Western blot analysis detected the expression of downstream proteins in the p53 signaling pathway. In vivo, experiments established a xenograft mouse model further to study the role of FAM72A in multiple myeloma.</p><p><strong>Results: </strong>FAM72A was upregulated in multiple myeloma bone marrow tissues. Compared to the OE-NC group, the OE-FAM72A group showed increased Mouse Double Minute 2 homolog (MDM2) expression, decreased p53 expression, increased cell proliferation, and decreased apoptosis. POU2F2 was identified as the upstream transcription factor for FAM72A. Compared to the si-NC group, the si-POU2F2 group exhibited decreased MDM2 expression, increased p53 expression, slowed cell proliferation, and increased apoptosis. Silencing POU2F2 could reverse the pro-proliferative effect of over-expressing FAM72A in U266 cells. <i>In vivo</i> experiments in a xenograft mouse model further studied the role of FAM72A in multiple myeloma.</p><p><strong>Conclusion: </strong>Overexpression of FAM72A promotes U266 cell proliferation, inhibits apoptosis, and reduces sensitivity to bortezomib by regulating the POU2F2/FAM72A/p53 signaling pathway.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"455-464"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Comprehensive Review on Preclinical Alzheimer's Disease Models: Evaluating their Clinical Relevance.","authors":"Virendra Kushwaha, Kantrol Kumar Sahu","doi":"10.2174/0113892010331845240802073645","DOIUrl":"10.2174/0113892010331845240802073645","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurological disorder that increases with age and must be treated immediately by worldwide healthcare systems. Internal neurofibrillary tau tangles and extracellular amyloid accumulation have been widely recognized as the primary causes of Alzheimer's disease. These degenerative age-related ailments are expected to proliferate exponentially as life expectancy rises. Experimental models of AD are essential for acquiring a deep knowledge of its pathogenesis and determining the viability of novel therapy options. Although there isn't a model that encompasses all the characteristics of real AD, these models are nonetheless highly helpful for the research of various modifications associated with it, even though they are only partially indicative of the disease circumstances being studied. Better knowledge of the advantages and disadvantages of each of the different models, as well as the use of more than one model to evaluate potential medications, would increase the effectiveness of therapy translation from preclinical research to patients. We outline the pathogenic characteristics and limitations of the main experimental models of AD in this review, including transgenic mice, transgenic rats, primates and non-primate models along with <i>in-vitro</i> cell culture models in humans. Additionally, it highlights the possible future of experimental modeling of AD and includes the co-morbid models.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"186-207"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential Serotonin 5-HT2A Receptor Agonist of Psychoactive Components of <i>Silene undulata</i> Aiton: LC-MS/MS, ADMET, and Molecular Docking Studies.","authors":"Maram B Alhawarri, Suleiman Olimat","doi":"10.2174/0113892010299804240324140017","DOIUrl":"10.2174/0113892010299804240324140017","url":null,"abstract":"<p><strong>Background: </strong>Silene undulata is historically used for inducing vivid and prophetic lucid dreams, but limited information exists on its phytochemical composition and potential pharmacological properties.</p><p><strong>Objective: </strong>This study aimed to investigate the phytochemical composition of <i>S. undulata</i> through LC-MS/MS analysis and explore its potential serotonergic activity, which could support and confirm the traditional use of <i>S. undulata</i> as a dream-inducing plant.</p><p><strong>Methods: </strong>LC-MS/MS analysis was conducted on <i>S. undulata</i> extract, identifying 51 phytochemicals, including norharman, harmalol, harmaline, harmine, and ibogaine alkaloids. ADMET and Molecular docking investigations were employed to assess the serotonergic potential of these compounds.</p><p><strong>Results: </strong>The analysis revealed the presence of <i>β</i>-carboline alkaloids, such as norharman, harmalol, harmaline, harmine, and ibogaine, within <i>S. undulata</i> extract. ADMET analysis showed that these compounds have a favourable pharmacokinetic properties. In addition, molecular docking investigations showed that harmaline (-8.90 Kcal/mol), harmalol (-8.56 Kcal/mol), and ibogaine (-8.75 Kcal/mol) exhibited binding affinities comparable to the control molecule, LSD (-9.14 Kcal/mol), indicating potential agonistic activity at serotonin 5-HT2A receptor.</p><p><strong>Conclusion: </strong>These findings provide insights into the potential therapeutic benefits of <i>S. undulata</i>, supporting its traditional use as a psychoactive plant. This study investigated the chemical constituents and potential serotonergic agonist activity of <i>S. undulata</i> for the first time. While promising, further research is necessary to uncover additional medicinal properties associated with the identified phytochemical components.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"260-275"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manaf AlMatar, Isil Var, Selin Saglam, Osman Albarri
{"title":"The Effectiveness of LISTEX<sup>TM</sup> P100 in Reducing the Biofilm of <i>Listeria</i> spp. on Steel, Plastic, and Galvanised Surfaces.","authors":"Manaf AlMatar, Isil Var, Selin Saglam, Osman Albarri","doi":"10.2174/0113892010299925240507063431","DOIUrl":"10.2174/0113892010299925240507063431","url":null,"abstract":"<p><strong>Background: </strong>Eliminating and managing <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i> biofilms is a significant problem for food safety, as listeriosis is among the worst foodborne illnesses.</p><p><strong>Methods: </strong>The Listex P100 bacteriophage's bactericidal and inhibitory properties have been investigated in relation to varying strains of vegetative cells and biofilms of <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i>.</p><p><strong>Results: </strong>The phage concentrations of 10<sup>9</sup> and 10<sup>10</sup> PFU/ml showed strong antibacterial activity against <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i> at both 10°C and 30°C (P<0.05). In 96- well microplate experiments, bacteriophage treatment inhibited biofilm development and reduced biofilm by up to 57.6% (P ≤ 0.05). When compared to controls, Listex P100 bacteriophage significantly reduced the populations of <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i> biofilms on the surfaces of galvanised, stainless steel, and plastic surfaces where holes were produced and the structure of Listeria spp. was disturbed.</p><p><strong>Conclusion: </strong>This study clearly demonstrated that <i>L. monocytogenes, L. welshimeri</i>, and <i>L. ivanovii</i> biofilms on galvanised, stainless steel, and plastic surfaces might be removed by using Listex P100 bacteriophage.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"539-549"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuhua Qiao, Rongbo Xue, Shijie Li, Jun Li, Chundong Ji
{"title":"Expression of LASS2 Can be Regulated by Dihydroartemisinin to Regulate Cisplatin Chemosensitivity in Bladder Cancer Cells.","authors":"Xuhua Qiao, Rongbo Xue, Shijie Li, Jun Li, Chundong Ji","doi":"10.2174/0113892010305651240514100129","DOIUrl":"10.2174/0113892010305651240514100129","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to investigate the potential of dihydroartemisinin to augment the efficacy of cisplatin chemotherapy through the modulation of LASS2 expression.</p><p><strong>Methods: </strong>TCMSP, CTR-DB, TCGA-BLC, and other databases were used to analyze the possibility of LASS2 as the target gene of dihydroartemisinin. Cell experiments revealed the synergistic effect of DDP and DHA. Animal experiments showed that DHA inhibited the growth of DDP-treated mice. In addition, WB, real-time PCR, and immunohistochemical analysis showed that DHA enhanced LASS2 (CERS2) expression in bladder cancer cells and DDP-treated mice.</p><p><strong>Results: </strong>LASS2 is associated with cisplatin chemosensitivity.LASS2 expression levels are different between BLC tissues and normal tissues. COX analysis showed that patients with high LASS2 expression had a higher cumulative overall survival rate than those with low LASS2 expression. The Sankey plot showed that LASS2 expression is lower in BLC tissues with more advanced stage and distant metastasis. The docking score of DHA and LASS2 reached the maximum value of -5.5259, indicating that DHA had a strong binding affinity with LASS2 targets. CCK8 assay showed that the most effective concentration ratio of DHA to DDP was 2.5 μg/ml + 10μg/ml. <i>In vivo</i> experiments showed that DHA inhibited tumor growth in cisplatin-treated mice. In addition, WB, RT-qPCR, and immunohistochemical analysis showed that DHA was able to enhance LASS2 expression in BLC cells and DDP-treated mice.</p><p><strong>Conclusion: </strong>The upregulation of LASS2 (CERS2) expression in bladder cancer cells by DHA has been found to enhance cisplatin chemosensitivity.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"525-538"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nai-Fang Chang, Pey-Shiuan Wu, Hsiang-Ju Yang, Ya-Min Zheng, Chih-Chien Lin
{"title":"Preparation and Evaluation of Nanoemulsion Formulation Containing Kojic Acid and Kojyl 3-aminopropylphosphonic Acid.","authors":"Nai-Fang Chang, Pey-Shiuan Wu, Hsiang-Ju Yang, Ya-Min Zheng, Chih-Chien Lin","doi":"10.2174/0113892010310230240615112928","DOIUrl":"10.2174/0113892010310230240615112928","url":null,"abstract":"<p><strong>Background: </strong>The kojyl 3-aminopropylphosphonic acid (KAP) was synthesized by kojic acid (KA) with a 3-aminopropylphosphonic acid. Which is more stable than KA and showed better skin penetration and anti-pigmentation efficacy in melanocytes. However, up till now, there have been no studies aimed at incorporating KAP into an emulsion system and evaluating its effectiveness.</p><p><strong>Objective: </strong>We develop a novel skin-lightening agent using KAP as the active ingredient and a low-cytotoxic nanoemulsion as the delivery system in this study.</p><p><strong>Method: </strong>The sorbitan monooleate and polysorbate surfactants with polyethylene glycol (PEG) co-surfactant were used to generate a nanoemulsion system.</p><p><strong>Result: </strong>The transparency and particle size stability over various storage times indicate that the formulated nanoemulsions are suitable for long-term storage. Besides, results demonstrate that the anti-pigmentation function of KA and KAP-containing nanoemulsions (NE-KA and NEKAP) evidently outperformed that of the non-packed KA and KAP group. Despite having the lowest concentration among other treatments, NE-KAP was able to reduce melanin content to approximately 80% of the blank.</p><p><strong>Conclusion: </strong>Our findings suggest that this newly developed nanoemulsion containing KAP could potentially serve as a sustainable alternative to hydroquinone for treating dermal hyperpigmentation disorders in future applications.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"608-616"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guoliang Mao, Wuqin Xu, Muhammad Jamil, Wei Zhang, Nanlin Jiao, Yinhua Liu
{"title":"Exploring the Diagnostic and Prognostic Predictive Values of Ferroptosis-related Markers in Lung Adenocarcinoma.","authors":"Guoliang Mao, Wuqin Xu, Muhammad Jamil, Wei Zhang, Nanlin Jiao, Yinhua Liu","doi":"10.2174/0113892010293337240312051931","DOIUrl":"10.2174/0113892010293337240312051931","url":null,"abstract":"<p><strong>Background: </strong>Lung Adenocarcinoma (LUAD), a common and aggressive form of lung cancer, poses significant treatment challenges due to its low survival rates.</p><p><strong>Aim: </strong>To better understand the role of ferroptosis driver genes in LUAD, this study aimed to explore their diagnostic and prognostic significance, as well as their impact on treatment approaches and tumor immune function in LUAD.</p><p><strong>Methods: </strong>To accomplish the defined goals, a comprehensive methodology incorporating both <i>in silico</i> and wet lab experiments was employed. A comprehensive analysis was conducted on a total of 233 ferroptosis driver genes obtained from the FerrDB database. Utilizing various TCGA databases and the RT-qPCR technique, the expression profiles of 233 genes were examined. Among them, TP53, KRAS, PTEN, and HRAS were identified as hub genes with significant differential expression. Notably, TP53, KRAS, and HRAS exhibited substantial up-regulation, while PTEN demonstrated significant down-regulation at both the mRNA and protein levels in LUAD samples. The dysregulation of hub genes was further associated with poor overall survival in LUAD patients. Additionally, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed aberrant promoter methylation patterns linked to the dysregulation of hub genes.</p><p><strong>Results & discussion: </strong>Furthermore, hub genes were found to participate in diverse oncogenic pathways, highlighting their involvement in LUAD tumorigenesis. By leveraging the diagnostic and prognostic potential of ferroptosis driver hub genes (TP53, KRAS, PTEN, and HRAS), significant advancements can be made in the understanding and management of LUAD pathogenesis.</p><p><strong>Conclusion: </strong>Therapeutic targeting of these genes using specific drugs holds great promise for revolutionizing drug discovery and improving the overall survival of LUAD patients.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"411-427"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}