Current molecular medicine最新文献

{"title":"Broad-Spectrum Vaccines: Challenges and Opportunities (A Systematic Review).","authors":"Swaroop Kumar Pandey, Sakshi Singh","doi":"10.2174/0115665240442393260519141157","DOIUrl":"https://doi.org/10.2174/0115665240442393260519141157","url":null,"abstract":"<p><strong>Background: </strong>Though advances in technologies have created an arena for multiple vaccinology platforms, the world population is still facing health challenges from the deadliest pathogens with a high mutation rate and their tremendous ability of immune evasion. Presently, there is a constant exigence to shift the vaccine development efforts from traditional vaccines to broad-spectrum vaccines for the effective prevention of contagious diseases.</p><p><strong>Materials and methods: </strong>Using several databases, a comprehensive systematic review of the literature pertinent to this article's discussion was carried out.</p><p><strong>Results: </strong>The present review article aims to provide a comprehensive understanding of the key characteristics and benefits of broad-spectrum vaccines over conventional vaccines. Further, it unveils the diverse range of broad-spectrum vaccines that have been developed so far, in addition to those that are currently under pre-clinical and clinical studies. Along with the illustration of the obstacles and possibilities concerned with their safety profile and viability of development, it also examines their potential for further research.</p><p><strong>Discussion: </strong>The development of broad-spectrum vaccines benefits greatly from the combination of several immunisation strategies. The scope and effectiveness of broadspectrum vaccinations have been shown to be greatly increased by combining various vaccination tactics, such as using multiple immunisation techniques, multivalent antigens, or heterologous boosters.</p><p><strong>Conclusion: </strong>The development and practical validation of broad-spectrum vaccines have been impeded thus far by biological complexity (rapid pathogen evolution, immune imprinting, host variability), logistical limitations, and regulatory frameworks intended for strain-specific products, leaving the majority of candidates at preclinical stages. To turn promising ideas into gradual, population-level protection, policy support, and focused research improving evaluation techniques, altering regulatory pathways, and advancing mRNA, multiepitope, and T-cell approaches are required.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263489","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":"Immunometabolic Reprogramming: A New Frontier in Cancer Immunotherapy.","authors":"Saeed Mohammadi, Mahmoud Darweesh, Mina Rahmati, Moosa Al-Hamadani, Milad Ahmadaghdami, Ahmed Al-Harrasi","doi":"10.2174/0115665240435650260516221100","DOIUrl":"https://doi.org/10.2174/0115665240435650260516221100","url":null,"abstract":"<p><p>The interaction between cellular metabolism and immune function, termed immunometabolism, has been regarded as a crucial determinant of anti-tumor immunity and the efficacy of cancer immunotherapy. Understanding the metabolic dependencies and vulnerabilities of various immune cell subsets and cancer cells is enabling researchers to study novel therapeutic strategies. These strategies aim to reprogram the metabolic landscape of the TME to enhance stronger anti-tumor immune responses and overcome resistance to current immunotherapies. This review provides a comprehensive overview of the fundamental principles of immunometabolism, detailing the key metabolic pathways and regulators in immune and cancer cells. We explore the distinct metabolic profiles of various immune cell subsets and how they are altered during an anti-tumor response. Furthermore, we discuss the metabolic hallmarks of cancer cells, considering variations across different cancer types. Then, we discuss how current immunotherapies, such as checkpoint inhibitors and CAR-T cell therapy, impact and are influenced by cellular metabolism. Finally, we highlight promising therapeutic opportunities for targeting immunometabolism, including metabolic inhibitors, modulators, and combination strategies. This review aims to introduce immunometabolic reprogramming as a new frontier to enhance the efficacy of cancer immunotherapy and improve patient outcomes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257543","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":"Study on the Cytotoxic Effects, Apoptosis Induction, Treatment Resistance, and Inflammation Caused by a Gold(III) Complex Containing 3,4-diaminobenzophenone and 2,3-butanedione Monoxime on the Esophageal Cancer Cell Line KYSE-30.","authors":"Xiaolong Lu, Mostafa Heidari Majd, Somaye Shahraki, Shang Li","doi":"10.2174/0115665240450237260518210845","DOIUrl":"https://doi.org/10.2174/0115665240450237260518210845","url":null,"abstract":"<p><strong>Background: </strong>Given the known therapeutic properties of gold compounds such as auranofin, this study aimed to evaluate the anticancer potential of a newly synthesized gold(III) Schiff base complex. We hypothesized that this complex could selectively induce apoptosis in cancer cells while minimizing inflammatory responses in normal cells.</p><p><strong>Methods: </strong>A gold(III) complex bearing a tetradentate Schiff base ligand was synthesized, and its cytotoxicity was assessed using MTT assay and sulforhodamine B staining. KYSE-30 esophageal cancer cells and NIH/3T3 normal fibroblasts were treated with the complex and compared to cisplatin. Gene expression analysis was performed to evaluate apoptotic and inflammatory genes.</p><p><strong>Results: </strong>The gold(III) Schiff base complex significantly inhibited KYSE-30 cell proliferation more effectively than cisplatin after 48 hours. Unlike cisplatin, it did not induce cytotoxicity in NIH/3T3 cells. The complex elevated the BAK1/Bcl-xL ratio by 2.22-fold, suggesting activation of the intrinsic mitochondrial apoptotic pathway, which was not observed with cisplatin. It also downregulated the anti-apoptotic Bcl-xL gene (0.662-fold) and the resistance-associated AKT1 gene (0.0544-fold). Both the gold(III) Schiff base complex and cisplatin activated the extrinsic apoptotic pathway via Caspase-3. Importantly, neither compound induced TNF-α expression, indicating no inflammatory response in normal cells.</p><p><strong>Discussion: </strong>These findings demonstrate that the gold(III) Schiff base complex selectively targets esophageal cancer cells through dual apoptotic pathways while sparing normal cells from cytotoxicity and inflammation. Its ability to suppress resistance-related genes further highlights its therapeutic promise.</p><p><strong>Conclusion: </strong>The gold(III) Schiff base complex represents a compelling alternative to cisplatin, offering enhanced anticancer efficacy, reduced toxicity to normal cells, and minimal inflammatory activation. Further investigation into its clinical potential is warranted.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223706","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":"GDF15 Aggravates Sepsis-Induced Coagulopathy and is Associated with PI3K/AKT/mTOR Signaling Changes.","authors":"Lihui Wang, Xiaoliang Ji, Qinglong Lu, Shimin Dong","doi":"10.2174/0115665240474141260519104154","DOIUrl":"https://doi.org/10.2174/0115665240474141260519104154","url":null,"abstract":"<p><strong>Introduction: </strong>The study was designed to explore the role of Growth Differentiation Factor 15 (GDF15) and its underlying mechanisms in coagulation dysfunction, the inflammatory response, and multi-organ damage using a rat model of cecal ligation and puncture (CLP)-induced sepsis.</p><p><strong>Methods: </strong>A CLP-induced sepsis model was established in Sprague-Dawley rats. Adenovirus vectors were used to overexpress or knockdown GDF15. A PI3K inhibitor (LY294002) was administered to specific groups. Serum levels of GDF15, apoptosis markers (cleaved-caspase3), endothelial injury markers (syndecan-1, heparan sulfate), coagulation markers (D-dimer), inflammatory cytokines (IL-6, TNF-α), and PI3K/AKT/mTOR phosphorylation were measured by ELISA. Coagulation parameters and platelet counts were assessed. Organ damage was evaluated via H&E staining of the liver, heart, and kidneys.</p><p><strong>Results: </strong>GDF15 levels were significantly elevated in CLP rats. High GDF15 levels were associated with increased cleaved-caspase3, syndecan-1, heparan sulfate, Ddimer, IL-6, and TNF-α; prolonged APTT, PT, and TT; decreased platelet count and fibrinogen (FIB); aggravated multi-organ damage; and enhanced PI3K, AKT, and mTOR phosphorylation. Silencing GDF15 or inhibiting PI3K with LY294002 reversed these effects, whereas GDF15 overexpression exacerbated them. The detrimental effects of GDF15 overexpression were attenuated by co-administration of LY294002.</p><p><strong>Discussion: </strong>GDF15 exacerbates coagulopathy, inflammatory responses, and multiorgan damage in septic rats, likely by activating the PI3K/AKT/mTOR signaling pathway. These results establish GDF15 as a potential mediator of sepsis pathophysiology and a therapeutic target warranting further investigation.</p><p><strong>Conclusion: </strong>The findings of this study suggest that GDF15 is associated with coagulation dysfunction, inflammatory responses, and multi-organ injury in septic rats, and these effects may involve modulation of the PI3K/AKT/mTOR signaling pathway. Regarding translational implications, GDF15 has potential as a biomarker, but human validation is required. It may represent a potential therapeutic target that warrants further investigation, and its clinical relevance requires confirmation in human studies. It is important to emphasize that these findings are derived from a preclinical rat model and may not directly translate to human sepsis.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204434","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":"Identification and Validation of Hub Ferroptosis‑Related Genes in Sepsis: An Integrated Bioinformatics and Experimental Study.","authors":"Fang Wan, Jiawei Ma","doi":"10.2174/0115665240478503260511103221","DOIUrl":"https://doi.org/10.2174/0115665240478503260511103221","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Sepsis is a life-threatening condition with heterogeneous pathogenesis. This study aimed to identify ferroptosis-related hub genes, construct their regulatory network, and evaluate their potential as biomarkers and therapeutic targets to elucidate the molecular mechanisms underlying sepsis heterogeneity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Transcriptomic data from 1,042 sepsis patients and 42 controls were integrated from public databases (GEO and ArrayExpress). Based on the expression of 47 ferroptosis-related genes, consensus clustering was performed to identify molecular subtypes. Differentially Expressed Genes (DEGs) between subtypes were identified and analyzed by functional enrichment. Key gene modules were identified using Weighted Gene Co-Expression Network Analysis (WGCNA), and hub genes were screened by intersecting WGCNA results with a Protein-Protein Interaction (PPI) network. An in silico-predicted multi-factor (TF-miRNA-mRNA) regulatory network was constructed using the starBase and Harmonizome databases. Key findings were preliminarily validated in a mouse model of E. coli-induced sepsis using quantitative real-time PCR (qRT-PCR).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Sepsis patients were stratified into two distinct ferroptosis-based subtypes (Cluster 1, n=702; Cluster 2, n=340). A total of 3,608 DEGs were identified, which were enriched in neutrophil activation, ubiquitination, and bacterial infection. WGCNA identified a key sepsis-associated module, leading to the selection of 21 hub genes from the co-expression network. In the septic mouse model, 9 of these genes (including ANK1, HMBS, and SIAH2) were significantly upregulated, and 2 genes (CA1, HBD) were downregulated in septic mice, providing preliminary experimental support for the bioinformatic findings. A comprehensive in silico-predicted regulatory network involving these 21 hub genes, 146 transcription factors, and 70 miRNAs was established as a resource for hypothesis generation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The identified hub genes and their regulatory network shed light on the role of ferroptosis in sepsis heterogeneity and pathogenesis. Genes such as SIAH2 and HMBS were differentially expressed between surviving and non-surviving patients, warranting further investigation as potential prognostic biomarkers in future studies. The constructed network identifies actionable targets (e.g., the E3 ligase SIAH2 and specific miRNAs) for therapeutic intervention. Limitations include the retrospective nature of the bioinformatic analysis and the need for further experimental validation of mechanistic roles.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study delineates a ferroptosis-associated gene signature and regulatory network in sepsis, providing a hypothesis-generating foundation for future research. The identified hub genes and their regulatory interactions warrant further investigation to explore their potential as prognostic biomarkers or thera","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197717","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":"Plasticity in Cancer Cells: The Master Engine of Therapeutic Resistance and Tumor Evolution.","authors":"Afza Ahmad","doi":"10.2174/0115665240472692260521045539","DOIUrl":"https://doi.org/10.2174/0115665240472692260521045539","url":null,"abstract":"<p><p>Cancer cell plasticity refers to the ability of cancer cells to change their phenotype and is one of the primary requirements for metastasis. It is considered one of the main contributors to intratumoral heterogeneity, a key factor in the development of cancer, and is known to alter responses and resistance to different forms of therapy. However, tumour cells are impaired in various cellular signalling pathways, such as mitogen-activated protein kinases, phosphoinositide-3-kinases, Wnt, Hedgehog, and Notch, as well as in epithelial-mesenchymal transition (EMT) and phenotypic plasticity. Cancer stem cells (CSCs) are considered an integral part of tumour plasticity, as they have the capacity to proliferate, differentiate, and initiate the growth of tumours. Recent studies suggest that targeting signals from the tumor microenvironment, plasticity-related pathways, and epigenetic regulators may offer promising therapeutic options to improve long-term response and reduce phenotypic dysregulation. This approach, which emphasizes plasticity as a primary biological driving force rather than a secondary one, allows cancer cells to change from an epithelial, mesenchymal, stem cell, or dormant state to a drug-resistant state in response to environmental stimuli. Taken together, these results suggest that cellular plasticity is important in tumour development and treatment failure. Therefore, targeting pathways associated with plasticity, modifying the tumour microenvironment, and using adaptive therapies may improve long-term tumour control.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136735","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 Real-world Pharmacovigilance Study of the FAERS Database: Safety Signals of Common Medications for Non-infectious Uveitis.","authors":"Xinle Zhang, Jing Wang, Ao Lu, Keyan Li, Guannan Su, Peizeng Yang","doi":"10.2174/0115665240430732260202212802","DOIUrl":"https://doi.org/10.2174/0115665240430732260202212802","url":null,"abstract":"<p><strong>Introduction: </strong>While a range of immunomodulatory medications are used for non-infectious uveitis (NIU), real-world pharmacovigilance data focusing on their safety profiles are lacking. This study aimed to evaluate the safety of commonly used medications for NIU and provide insights into their associated adverse events (AEs).</p><p><strong>Methods: </strong>Data on medications used for NIU (from the fourth quarter of 2014 to the second quarter of 2024) were obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were calculated for AEs signal detection. A significant safety signal was defined only when it was concurrently identified by both algorithms.</p><p><strong>Results and discussion: </strong>Among ten medications for NIU, adalimumab accounted for the highest number of AEs reports (N=5,842), followed by infliximab (N=1,199), prednisone (N=749), and methotrexate (N=427). Common AEs were observed in the present study. For instance, AEs of infections (N=293) and endocrine disorders (N=47) were reported in prednisone. We also found several AEs which had not been reported in NIU patients before, with splenomegaly as an example (ROR 95% CI lower bound: 4.66; IC025: 1.35; P<0.001). Moreover, some rare AEs were identified. The disproportionality analysis identified a significant signal for neoplasms associated with biologics (ROR 95% CI lower bound:1.42; IC025: 0.66; P<0.001). This disproportionality analysis provides real-world evidence for a more comprehensive safety spectrum of NIU medications.</p><p><strong>Conclusion: </strong>Medications for NIU cause AEs across multiple systems. This study provides valuable insights into the similarities and differences in the safety of NIU medications, including common, novel, and rare AEs. Clinicians should carefully weigh the visual benefits against risks and tailor individual treatment plans for patients with NIU.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142899","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":"Causal Associations Between Three Types of Anemia and Pulmonary Tuberculosis: A Bidirectional Mendelian Randomization Study.","authors":"Detian Liu, Yuwei Lai, Yuan Zhou, Wei Zhuang","doi":"10.2174/0115665240441085260216093437","DOIUrl":"https://doi.org/10.2174/0115665240441085260216093437","url":null,"abstract":"<p><strong>Introduction: </strong>Anemia and pulmonary tuberculosis (PTB) are major global public health problems. Available observational studies have suggested a potential link between them. However, the causal relationship between anemia and PTB remains uncertain. Therefore, our study aims to investigate the causal relationship between different anemia types and PTB by bidirectional Mendelian Randomization (MR) analysis.</p><p><strong>Methods: </strong>Pernicious Anemia (PA), Iron Deficiency Anemia (IDA), Aplastic Anemia (AA), and PTB genetic summary data were obtained from several independent large Genome-Wide Association Studies (GWAS). The Inverse Variance Weighting (IVW) method was used as the primary method for MR analysis, complemented by methods such as weighted median and MR-Egger to enhance the robustness of the MR analysis. In addition, sensitivity analyses and heterogeneity tests were conducted to assess the robustness of the results and identify potential sources of heterogeneity.</p><p><strong>Results: </strong>Our study showed a causal relationship between PA and PTB (IVW: OR = 1.135, 95% CI = 1.035-1.244, p = 0.007). However, there was no evidence of a causal relationship between IDA and PTB or between AA and PTB. In addition, reversedirection MR analysis found no evidence of causal effects between PTB and these three anemias.</p><p><strong>Discussion: </strong>This study identified a significant positive causal effect of PA on PTB. Therefore, it is recommended to strengthen screening for PTB-related indicators in PA patients in clinical practice. Additionally, in regions with high PTB incidence, PA can be designated as a risk warning indicator for PTB. Vitamin B12 malabsorption, a characteristic feature of PA, may play a crucial role in the causal relationship between PA and PTB.</p><p><strong>Conclusion: </strong>Our study is the first to explore the genetic causality between anemia and PTB, identifying PA as a significant genetic risk factor for PTB. Future studies are needed to elucidate the underlying mechanisms and provide new insights into the prevention and treatment of PTB.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142884","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":"Identification of Potential Plasma Biomarkers of Abdominal Aortic Aneurysm Using a Metabolomics Approach.","authors":"Wei Wang, Zhaoran Chen, Xiaoyue Tang, Xuebin Wang, Lianglin Wu, Wenxuan Xiang, Zhiwen Zhang, Hai Feng, Jianqiang Wu, Yuehong Zheng","doi":"10.2174/0115665240435737260306084312","DOIUrl":"https://doi.org/10.2174/0115665240435737260306084312","url":null,"abstract":"<p><strong>Objective: </strong>In the aging population, abdominal aortic aneurysm (AAA) is a widespread and serious disease. Currently, there are no available biomarkers for diagnosing or treating AAA with drugs in clinical use. Uncovering the metabolic signatures of AAA may provide new insights into its pathogenesis and facilitate the identification of novel metabolic biomarkers.</p><p><strong>Methods: </strong>In the present study, we applied high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based metabolomics to analyze plasma samples from 76 AAA patients and 72 controls.</p><p><strong>Results: </strong>A total of 115 differentially abundant metabolites were identified, and these metabolites were mainly involved in retinol metabolism, glutathione metabolism, purine metabolism, D-amino acid metabolism, pantothenate and CoA biosynthesis, porphyrin metabolism, and sphingolipid metabolism. After biomarker screening in the discovery cohort and biomarker verification in the validation cohort, 28 potential metabolite biomarkers of AAA were identified. Further examination indicated that three metabolites, including 5-Delta-Hydroxybutyl Hydantoin, 2-Amino-4-[(2- hydroxy-1-oxopropyl) amino] butanoic acid, and 15(R),19(R)-hydroxy PGF2, showed remarkable sensitivity and specificity in diagnosing AAA, with AUC values of 0.997, 0.989, and 0.978, respectively.</p><p><strong>Discussion: </strong>This metabolomics study revealed distinct plasma metabolic profiles in AAA patients compared to controls, identifying 115 differentially abundant metabolites. These metabolites were primarily enriched in pathways including retinol metabolism, glutathione metabolism, and purine metabolism. Three metabolites-5-delta-hydroxybutyl hydantoin, 2-amino-4-[(2-hydroxy-1- oxopropyl) amino] butanoic acid, and 15(R),19(R)-hydroxy-PGF2α-were identified as novel potential biomarkers and showed excellent diagnostic performance in combination. The findings suggest that dysregulation of retinol metabolism, implicated in vascular homeostasis, and glutathione metabolism, linked to oxidative stress and ferroptosis, may play roles in AAA pathogenesis. Alterations in purine metabolism further support the involvement of inflammatory and oxidative processes. While these biomarkers show promise, their functional roles in AAA and clinical utility require validation in larger, multicenter prospective studies.</p><p><strong>Conclusion: </strong>This study identified potential novel plasma biomarkers of AAA, which could contribute to the discovery of diagnostic biomarkers and therapeutic targets for this disease.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142944","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":"Sappanone A Ameliorates Cisplatin-induced Cytotoxicity Via Nrf2/HO-1 Signaling in HK-2 Cells.","authors":"Guona Zheng, Yang Liu, Bingjie Li, Fan Yang, Lin Kang","doi":"10.2174/0115665240425625251221125404","DOIUrl":"https://doi.org/10.2174/0115665240425625251221125404","url":null,"abstract":"<p><strong>Objective: </strong>To explore the role of the Nrf2 signaling pathway in sappanone A (SA)-mediated protection against cisplatin (CP)-induced renal injury, we investigated the impact of Nrf2 knockdown on cell apoptosis, oxidative stress, NF-κB activation, and IL-1β release in human renal proximal tubular cell line HK-2 cells.</p><p><strong>Materials and methods: </strong>siRNA-mediated knockdown of the Nrf2 gene was performed in HK-2 cells. Oxidative stress markers, including malondialdehyde (MDA) and hydroxyl radical (•OH), were quantified using colorimetric assays. Apoptotic cell death was evaluated by both TUNEL staining and flow cytometry. Western blot analysis was employed to detect protein expression levels of Nrf2, heme oxygenase-1 (HO-1), p65, and phosphorylated p65 (p-p65). The level of interleukin-1β (IL-1β) in cell culture supernatants was measured using ELISA.</p><p><strong>Results: </strong>Down-regulation of Nrf2 significantly suppresses SA's protective effect against CP-induced oxidative stress, as reflected by increased MDA and •OH as well as reduced the expression of HO-1 in HK-2 cells. Nrf2 depletion eliminates SA's capacity to reduce cell apoptosis. SA attenuates CP-induced phosphorylation of NF- κB p65 (p-p65), but this inhibition is reversed by Nrf2 depletion. ELISA analysis further demonstrates that Nrf2 knockdown elevates IL-1β secretion in HK-2 cells, indicating enhanced inflammatory response upon Nrf2 loss.</p><p><strong>Discussion: </strong>SA, an active compound from Caesalpinia sappan L. with antioxidant, anti-inflammatory, and anti-apoptotic properties, mitigates CP-induced nephrotoxicity in HK-2 cells by suppressing oxidative stress, inflammation, and apoptosis through activating the Nrf2 pathway (enhancing Nrf2 and HO-1 expression), as confirmed by experiments showing SA reduces biomarkers of these processes and that Nrf2 silencing abolishes such effects, aligning with classical Nrf2 activation patterns.</p><p><strong>Conclusion: </strong>Nrf2-mediated inhibition of oxidative stress, apoptosis, and inflammation contributes to the protective effect of Sappanone A against cisplatininduced cytotoxicity in HK-2 cells.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143025","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}