Biochemistry Research International最新文献

{"title":"Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From Multidatabase Analysis.","authors":"Vikrant Kumar, Nawaid Hussain Khan, Shashi Nandar Kumar, Neeraj Mahajan, Wafa Aziz, Vinay Kumar, Chaitenya Verma","doi":"10.1155/bri/6647501","DOIUrl":"10.1155/bri/6647501","url":null,"abstract":"<p><strong>Objective: </strong>Colon adenocarcinoma (COAD) remains a leading cause of cancer-related mortality, necessitating reliable prognostic biomarkers. This study explored the potential prognostic role of C-C motif chemokine ligand 3 (CCL3) and its association with immune-related signatures in COAD.</p><p><strong>Methods: </strong>Multiple publicly accessible databases, including TCGA, GEPIA2, UALCAN, TIMER, and Kaplan-Meier (KM) plotter, were used to examine the expression and prognostic profiles of CCL3 in various cancers. The association between CCL3 expression and clinical stage, immune infiltration, and immune gene markers was investigated using TIMER, GEPIA2, and TISIDB databases. Furthermore, we conducted functional enrichment analyses (GO and KEGG) of genes coexpressed with CCL3, assessed methylation status using OncoBD and MEXPRESS, and developed a gene-miRNA interaction network using miRWalk to elucidate their potential roles in COAD.</p><p><strong>Results: </strong>The expression of CCL3 was significantly upregulated in COAD and most other malignancies. Furthermore, high CCL3 expression was significantly associated with poor overall survival (OS) and relapse-free survival (RFS), with a univariate HR = 1.52 (95% CI: 1.12-2.06, <i>p</i> < 0.01). Multivariate Cox regression confirmed CCL3 as an independent prognostic factor after adjusting for the TNM stage, age, gender, and grade (adjusted HR = 1.42, 95% CI: 1.05-1.92, <i>p</i> = 0.023). CCL3 showed strong positive correlations with immune cell infiltration, particularly macrophages (Cor = 0.72, <i>p</i> < 0.001) and neutrophils (Cor = 0.74, <i>p</i> < 0.001), suggesting its role in shaping an immunosuppressive tumor immune microenvironment (TIME). Additionally, preliminary correlations indicate that high CCL3 may be associated with chemotherapy resistance.</p><p><strong>Conclusion: </strong>This study suggests that CCL3 could serve as a potential prognostic marker for COAD and other cancers. Because CCL3 expression was strongly associated with immune modulation within the tumor microenvironment, this pointed out that CCL3 could serve as a promising therapeutic target with significant implications for immunotherapy and chemotherapy response.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"6647501"},"PeriodicalIF":2.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13090570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the In Vitro and In Vivo Neuroprotective Effects of Several Polyphenolics on LPS-Induced Neuroinflammation.","authors":"Mona Elkhatieb, Rasha A Radwan, Doaa Abou El-Ezz, Christine Adel Sedky, Ulrike Breitinger, Nabila Hamdi, Amira Emad Abdelaziz, Sarah Atef Fahim, Ahmed M Hafez","doi":"10.1155/bri/1541212","DOIUrl":"10.1155/bri/1541212","url":null,"abstract":"<p><p>Oxidative stress and neuroinflammation are key components in neurodegenerative diseases, where early intervention using natural treatments may offer neuroprotective effects. This study shows that isoliquiritigenin (ISL), hesperidin (HES), and curcumin (CUR) can mitigate lipopolysaccharide (LPS)-induced neuroinflammation and oxidative stress in vitro and in vivo. The compounds were initially tested for cytotoxicity and found to reduce nitric oxide (NO) production, especially CUR and ISL. They were able to restore antioxidant enzyme activities both in vivo and in vitro. All treatments reduced inducible nitric oxide synthase (iNOS) expression compared to the untreated LPS control group. Behavioral assessments indicated that LPS impaired spatial and nonspatial memory, but treatments improved cognitive performance. Biomarker analyses revealed that ISL, HES, and CUR reduced the interleukin (IL)-1β and nuclear factor erythroid 2-related factor 2 (Nrf2) ratio in the hippocampus. Moreover, they decreased the level of caspase-3 demonstrated by western blotting and tumor necrosis factor-α (TNF-α) level. Thereby they inhibited LPS elicited apoptosis. Likewise, their anti-inflammatory effects were illustrated in the histopathological examination. Furthermore, they decreased the expression of amyloid-β. The study reinforces the potential of these natural compounds as protective and therapeutic cost-effective alternatives for managing neuroinflammation and neurodegeneration.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"1541212"},"PeriodicalIF":2.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13071770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Effect of Low-Density Lipoprotein Cholesterol on Chronic Kidney Disease: A Mendelian Randomization Study.","authors":"Dongming Zhou, Kangchao Zheng, Suwei Zhang, Bingbing Zheng","doi":"10.1155/bri/3548900","DOIUrl":"10.1155/bri/3548900","url":null,"abstract":"<p><strong>Background: </strong>While dyslipidemia is associated with chronic kidney disease (CKD), conventional observational studies cannot establish causality, and previous Mendelian randomization (MR) findings on low-density lipoprotein cholesterol (LDL-C) and CKD remain inconsistent.</p><p><strong>Objective: </strong>To further investigate the causal relationship between LDL-C and CKD using MR and evaluate its independence.</p><p><strong>Methods: </strong>We employed a two-sample and multivariable MR (MVMR) framework. Initially, two-sample and reverse MR analyses were performed for four lipid traits on CKD using genetic data from the IEU Open GWAS and the UK Biobank separately, with a Bonferroni-corrected significance threshold of <i>p</i> < 0.0125. Subsequently, MVMR was conducted to assess the independent effect of LDL-C after adjusting for other lipid traits (<i>p</i> < 0.05). Finally, an MVMR model incorporating LDL-C, smoking, alcohol consumption, and body mass index (BMI) was fitted to test the independence from these lifestyle confounders, followed by a sensitivity analysis with linkage disequilibrium-based confounder filtering to verify robustness.</p><p><strong>Results: </strong>Two-sample MR showed a significant causal effect of LDL-C on increased CKD risk (IEU source: OR = 1.13, 95% CI: 1.03-1.23, <i>p</i> < 0.01; consistent results from UK Biobank), with no evidence of reverse causation. MVMR confirmed the independence of this association: LDL-C remained significantly associated with CKD after adjusting for other lipid traits (OR = 1.21, 95% CI: 1.08-1.35, <i>p</i> = 0.0007) and after further adjustment for BMI, smoking, and alcohol (OR = 1.14, 95% CI: 1.04-1.25, <i>p</i> = 0.068). The effect direction remained consistent in the stringent sensitivity analysis.</p><p><strong>Conclusion: </strong>LDL-C may be an independent risk factor for CKD, the independence of which warrants further validation.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"3548900"},"PeriodicalIF":2.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis Reveals Potential Molecular Targets in Juvenile Dermatomyositis.","authors":"Chunyan Chen, Haifa Qiao","doi":"10.1155/bri/1147461","DOIUrl":"10.1155/bri/1147461","url":null,"abstract":"<p><p>Juvenile dermatomyositis (JDM) is a rare autoimmune disease primarily affecting children, characterized by muscle weakness and skin lesions. This study identifies 145 genes significantly associated with JDM through differential gene expression analysis, weighted gene coexpression network analysis (WGCNA), protein-protein interaction network analysis, and miRNA and transcription factor (TF) prediction, using blood and muscle microarray sequencing datasets. Functional enrichment analysis indicates that these genes are involved in crucial biological processes, including cytokine-mediated signaling, extracellular matrix organization, and immune response. Further analysis reveals key TFs (<i>e.g.,</i> STAT1 and NFKB1) and miRNAs (<i>e.g.,</i> hsa-miR-127-3p and hsa-miR-17-5p) that may regulate the expression of these critical genes in JDM. The findings provide new insights into the molecular mechanisms of JDM and offer potential targets for future diagnostic and therapeutic strategies.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"1147461"},"PeriodicalIF":2.9,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12966348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Turning Agricultural Waste Into Enzymatic Treasure: Bromelain Stability in Pineapple Crown and Peel Waste From Subang District, Indonesia.","authors":"Nyi Mekar Saptarini, Driyanti Rahayu, Danni Ramdhani, Delphine Wirawan, Virgiana Keisha Rajabi Johni Sudirman","doi":"10.1155/bri/7470038","DOIUrl":"10.1155/bri/7470038","url":null,"abstract":"<p><p>Bromelain is one of the protease enzymes found in all parts of pineapple (<i>Ananas comosus</i> (L.) Merr.), including the crown and peel. This enzyme has been widely used in various fields of life, including the food industry, health, pharmaceuticals, and cosmetics. However, pineapple processing often focuses on the flesh of the fruit, leaving behind substantial agricultural waste, such as crown and peel waste. The waste is often collected and stored before being used, causing the bromelain enzyme to decrease or even dissipate. Therefore, this study aims to determine the effect of time and the condition of storage of pineapple crown and peel waste on total protein content and protease activity. The extracted bromelain was precipitated with ethanol and then dried, and total protein content and protease activity were determined. The results showed that pineapple crown and peel waste can be stored for 7 days at 29 ± 1°C and humidity of 70 ± 2% and 20 days at 4 ± 0.5°C and humidity of 40 ± 2%, respectively. The total protein content and protease activity were 169.94 ± 2.68 μg/mL and 46.35 ± 0.69 IU/mg for crown bromelain, while those for peel bromelain were 229.75 ± 15.61 μg/mL and 29.10 ± 1.98 IU/mg, respectively. In conclusion, pineapple crown waste has the potential to be developed as a source of bromelain.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"7470038"},"PeriodicalIF":2.9,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12947115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Prognostic Biomarkers and Key Pathways in Renal Clear Cell Carcinoma: A Pilot Study Using Integrated miRNA and Gene Expression Analysis.","authors":"Hamed Manoochehri, Kosar Mirzaee, Amir Taherkhani, Mahmoud Gholyaf","doi":"10.1155/bri/3213941","DOIUrl":"10.1155/bri/3213941","url":null,"abstract":"<p><strong>Background and objective: </strong>Renal clear cell carcinoma (RCCC) stands out as a prevalent and aggressive subtype of kidney cancer characterized by a challenging prognosis. The need to enhance patient outcomes in RCCC underscores the significance of identifying prognostic biomarkers and therapeutic targets. MicroRNAs (miRNAs) and the signaling pathways orchestrating RCCC pathogenesis emerge as promising candidates for such endeavors.</p><p><strong>Methods: </strong>This study utilized publicly available gene expression data to compare miRNA profiles in nine RCCC and 11 normal kidney tissues. Rigorous bioinformatics analyses were employed to identify differentially expressed miRNAs and their associated gene targets. Prognostic significance was assessed, and a protein-protein interaction network was constructed to highlight pivotal RCCC hub genes. The expression and prognostic value of key hub genes and miRNAs were further validated in independent cohorts, including the GEO dataset GSE76351 and the TCGA-KIRC cohort via the Kaplan-Meier plotter. Expression of RUNX2 was confirmed using real-time PCR in five cancer and five normal renal tissues.</p><p><strong>Results: </strong>Fifteen DEMs were identified alongside 74 hub genes. The downregulation of miR-26a-1-3p, miR-144-3p, and miR-144-5p was associated with a poorer prognosis in RCCC. The overexpression of CDK1 and RUNX2 was validated in an independent GEO dataset and correlated with decreased patient survival in the TCGA-KIRC cohort. Furthermore, a statistically significant but modest inverse association was observed between miR-26a-1-3p and RUNX2 expression, indicating a possible miRNA-mRNA relationship. Significant enrichment was observed in pathways related to PI3K-Akt, MAPK, apoptosis, and cell cycle. The overexpression of RUNX2 was confirmed in our patient samples (<i>p</i> value< 0.05).</p><p><strong>Conclusion: </strong>This multistep validation study confirms that specific miRNAs and hub genes, particularly the miR-26a-1-3p/RUNX2 axis, are potential prognostic indicators in RCCC. A comprehensive understanding of these biomarkers and their enriched signaling pathways provides deeper insight into the molecular underpinnings of RCCC, uncovering potential therapeutic opportunities.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"3213941"},"PeriodicalIF":2.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Expression, Docking and Machine Learning in Malaria Drug Discovery: A Systematic Review.","authors":"Reuben Samson Dangana, Israel Ehizuelen Ebhohimen, Samson Anjikwi Malgwi, Samuel Chima Ugbaja, Moses Okpeku","doi":"10.1155/bri/2724332","DOIUrl":"10.1155/bri/2724332","url":null,"abstract":"<p><strong>Background: </strong>Malaria remains a significant and worldwide health threat with increasing resistance to current treatments, stimulating the demand for innovative approaches in pursuing drug discovery. This systematic review integrates the progress made from 2014 through 2024 regarding molecular methods like gene expression profiling, molecular docking and machine learning to understand the biology of <i>Plasmodium</i> and identify new drug targets and compounds, focusing on herbal remedies and computational methods.</p><p><strong>Methodology: </strong>Several studies were found using a PRISMA-guided search of PubMed, Scopus and Web of Science (64 studies found). The data extracted were gene expression outcomes, docking affinities, ML models and experimental validations (in vitro/in vivo).</p><p><strong>Results: </strong>Molecular docking emerged as the dominant technique (32.37%), followed by in vitro antiplasmodial assays (14.39%), ADMET profiling (10.79%) and gene expression studies (3.60%). RNA-seq analysis revealed key host and parasite genes modulated by herbal treatments, including those involved in apoptosis and inflammation. Notably, compounds like isorhamnetin and myricetin 3-O-glucoside showed exceptionally high binding affinities to <i>Plasmepsin II</i> and <i>Plasmodium falciparum</i> lactate dehydrogenase (PfLDH) (ΔG < -13 kcal/mol). ML models like random forest and support vector machine (SVM) exhibited high predictive results (AUC value up to 0.87) for bioactivity and resistance patterns that showed flavonoids (quercetin) and terpenoids (eugenol) as good candidates. Pathways that are often attacked are haemoglobin degradation, glycolysis, pyrimidine metabolism and protein synthesis.</p><p><strong>Conclusion: </strong>Multiomics, docking and ML integration improve the target identification and prioritise the compounds. This review illustrates the great potential of molecular techniques for the development of drugs against antimalarial helicases that are not resistant to drug therapy. However, in vivo data holes and methodology inconsistency limit clinical translation. Future work should include standardisation of protocols and studies of synergistic combinations of phytochemicals.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"2724332"},"PeriodicalIF":2.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligand-Based Pharmacophore Mapping and Virtual Screening for the Search of Biguanide-Like Molecules With Antidiabetic Potentials Targeting Liver Kinase B1.","authors":"Rumman Reza, Md Nazmus Samdani, Niaz Morshed, Raihana Haque Jebin, Imtiaz Ahmed, Md Selim Reza","doi":"10.1155/bri/8369459","DOIUrl":"10.1155/bri/8369459","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a state where the body's glucose metabolism is compromised. AMP-activated protein kinase, or AMPK, has an important part to play in glucose metabolism, and the liver kinase B1 (LKB1) protein functions as a major upstream kinase for AMPK activation, thereby making it appealing therapeutic targets for treating and preventing T2DM. Drug resistance cases for biguanides like metformin is a serious concern and pose great threat to treatment success for diabetic patients. Thus, the hunt for biguanide-like small molecules with enhanced insulin sensitizing potentials is necessary. In the present study, interaction between LKB1 and biguanides such as phenformin, metformin, and buformin has been thoroughly assessed using computational tools. Ligand-based pharmacophore mapping of 29,000 phytochemicals collected from NPASS database was carried out. The screening was conducted to hunt novel antidiabetic compounds targeting LKB1 pathway to improve insulin sensitivity in T2DM. Molecular docking of 31 phytochemicals with good pharmacophore fit scores was then carried out to identify hit compounds. ADMET analysis was also utilized to screen down compounds. dragmacidin D, dioncopeltine A, saussureamine C, and agelastatin D have good binding affinities and acceptable ADMET parameters. Molecular dynamics simulation was carried out to confer the stability of ligand-protein complex under simulated human body conditions. After 100 nanoseconds molecular dynamics simulation, the LKB1 protein complexed with compounds (saussureamine C and agelastatin D) was found to be stable. The results of the current study can be useful in developing antidiabetic medications with enhanced insulin sensitization activates superior to those available in market.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"8369459"},"PeriodicalIF":2.9,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12917864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NADPH-Related Enzymes and Cancer: Facts and Insights Into the Application of Immunohistochemistry.","authors":"Camila M Scudeler, Keila Samantha da Silva, Rafaela V N Silva, Adilha M R Micheletti, Karen B Ribeiro, Juliana Reis Machado, Régia C P Lira","doi":"10.1155/bri/1853546","DOIUrl":"10.1155/bri/1853546","url":null,"abstract":"<p><p>During tumorigenesis and metastasis, cancer cells initiate antioxidant defense mechanisms to prevent irreversible damage, thereby sustaining tumor growth. The functionality of reactive oxygen species (ROS)-scavenging proteins is dependent on nicotinamide adenine dinucleotide phosphate (NADPH), which is regulated by specific metabolic enzymes, which are described as potential biomarkers of cancer aggressiveness. Immunohistochemistry (IHC) is one of the most accessible and widely utilized techniques to augment the pathological diagnosis of cancer. Hence, this review addresses the protein expression of NADPH-related enzymes, as assessed by IHC, and their associations with human cancer progression factors (overall survival, tumor staging, metastasis, and recurrence). Studies indicate that glucose-6-phosphate dehydrogenase (G6PD), along with malic enzymes and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), represents the most pertinent enzymes examined through IHC concerning cancer aggressiveness. The immunolabeling method produced consistent results for this group of enzymes, which might lead to successful application in predicting tumor prognosis. Other NADPH-related enzymes, such as glutamate dehydrogenase (GDH), aldehyde dehydrogenase 1 (ALDH1), and dihydrofolate reductase (DHFR), deserve more extensive investigation to elucidate their potential as cancer biomarkers via IHC.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"1853546"},"PeriodicalIF":2.9,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noncatalytic Functions Are Required for MPO and PON1 in Modulating the Involvement of Monocytes and Endothelial Cells in Atherosclerosis.","authors":"Yong Li, Yunkai Liu, Yi Cheng","doi":"10.1155/bri/8149388","DOIUrl":"10.1155/bri/8149388","url":null,"abstract":"<p><p>High-density lipoproteins (HDLs) are deeply implicated in atherosclerosis. HDL, myeloperoxidase (MPO), and paraoxonase-1 (PON1) form a functional ternary complex where PON1 partially inhibits the MPO activity, and MPO in turn partially inactivates PON1. The activity of MPO is dependent on the concentration of hydrogen peroxide, but the extremely low concentrations of hydrogen peroxide in serums severely constrain MPO activity. PON1 has the activities of organophosphatase, arylesterase, and thiolactonase, but these hydrolase activities are extraneous to antioxidative stress. Thus, we proposed that MPO and PON1 may be involved in atherosclerosis by acting as proteins, rather than enzyme activities. Cholesterol efflux assay, ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux, and LCAT activity assay were performed. The effect of MPO, PON1, and serums from the individuals with ASCVD and healthy individuals on cholesterol efflux of human acute monocytic leukemia cell line (THP-1 cells) was compared. Noncatalytic functions of MPO and PON1 were analyzed using recombinant proteins and neutralizing antibodies. Wound healing assay and tube formation assay were used to analyze noncatalytic functions of MPO and PON1 in modulating the involvement of human umbilical vein endothelial cells (HUVECs). We found that MPO protein decreased the cholesterol efflux; by contrast, PON1 protein increased the cholesterol efflux of THP-1 cells. Importantly, MPO antibody partially restored cholesterol efflux, but PON1 antibody partially reduced cholesterol efflux of THP-1 cells. Moreover, ABCA1 was necessary for controlling the involvement of MPO and PON1 in modulating cholesterol efflux of THP-1 cells. There existed the confrontations between the noncatalytic functions of PON1 and MPO in migration of endothelial cells. Instead, MPO protein enhanced the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin of HUVECs; nonetheless, PON1 protein reduced the expression of these adhesion molecules. Of note, PON1 protein was unable to balance out the induction of MPO protein for these adhesion molecules in that the expression of these adhesion molecules generated by the combination of MPO protein and PON1 protein was similar to that of MPO. The activation of THP-1 cells induced by MPO protein directly impaired in vitro microvascular structure via increasing the expression of IL-6 and TNFα regulated by NF-κB p65 of THP-1 cells. Together, the noncatalytic functions entail MPO and PON in modulating the involvement of monocytes and endothelial cells in atherosclerosis.</p>","PeriodicalId":8826,"journal":{"name":"Biochemistry Research International","volume":"2026 ","pages":"8149388"},"PeriodicalIF":2.9,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12907566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}