Cell Biochemistry and Biophysics最新文献

{"title":"Identification of circRNA-Based Biomarkers and ceRNA Mechanism in Non-Small Cell Lung Cancer.","authors":"Zhengjia Liu, Xiyu Liu, Cong Yin, Zihao Liu, Haixiang Yu","doi":"10.1007/s12013-025-01753-y","DOIUrl":"10.1007/s12013-025-01753-y","url":null,"abstract":"<p><p>We aimed to identify circRNA as a biomarker in non-small cell lung cancer (NSCLC) and explore the underlying mechanism. circRNA and mRNA data were retrieved from GEO database. A series of bioinformatics analyses including differentially expressed analysis, weighted gene co-expression network analysis (WGCNA), Random Forest, and support vector machine algorithm were applied to identify the key circRNAs in NSCLC. ROC curves were used to evaluate and distinguish the roles of key circRNAs in cancer. The expression levels of circRNAs were validated via qPCR analysis. Finally, a ceRNA network was constructed. Herein, si-hsa_circ_0084443 was transfected into NSCLC cells to investigate its function in NSCLC. Five circRNAs (hsa_circ_0049271, hsa_circ_0029426, hsa_circ_0084443, hsa_circ_0015278, and hsa_circ_0024731) were identified as biomarkers in NSCLC. They exhibited potent diagnostic ability in identifying NSCLC, with AUC > 0.85. qPCR results suggested that hsa_circ_0049271, hsa_circ_0029426, and hsa_circ_0015278 were significantly downregulated and hsa_circ_0084443 and hsa_circ_0024731 were significantly upregulated in tumor tissue compared with the levels in normal tissues (P < 0.05). A ceRNA network was finally constructed. Knockdown of hsa_circ_0084443 inhibited cell growth, migration, invasion, and colony formation, and promoted apoptosis in NSCLC cell line. Five circRNAs were identified as biomarkers and demonstrated abnormal expression in NSCLC. Furthermore, ceRNA network was constructed, which can aid the mechanism exploration in the future.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3773-3785"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Berberine and Cyperus Rotundus Extract Nanoformulations Protect the Rats Against Staphylococcus-Induced Mastitis via Antioxidant and Anti-Inflammatory Activities: Role of MAPK Signaling.","authors":"Hanan A Edres, Ingi H Elmassry, Mohamed A Lebda, Sarah I Othman, Dina R S Gad El-Karim, Hassan A Rudayni, Sawsan Kh M Ebied, Ahmed A Allam, Aml E Hashem","doi":"10.1007/s12013-025-01680-y","DOIUrl":"10.1007/s12013-025-01680-y","url":null,"abstract":"","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3983"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel Neuraminidase Inhibitors as Potential Anti-Influenza Agents: Virtual Screening, Molecular Docking, in vitro Validation and Molecular Dynamic Simulation Studies.","authors":"Junya Liu, Jinbo Niu, Lihua Xu, Huiru Zhao","doi":"10.1007/s12013-025-01734-1","DOIUrl":"10.1007/s12013-025-01734-1","url":null,"abstract":"<p><p>The influenza virus causes approximately hundreds of thousands of deaths annually. Coupled with the emergence of drug resistance, there is an urgent need to develop new drugs for the treatment of influenza. Neuraminidase (NA) has long been recognized as a valid drug target for anti-influenza therapy. Herein, in order to identify potential NA inhibitors with novel structures, we employed a structure-based virtual screening strategy to screen a library containing 1.6 million compounds. Based on XP docking score and free energy calculation results, the three compounds E570-1769, K788-4718, and C071-0424 were selected that may have better binding affinity for the NA protein compared to oseltamivir. Amongst, E570-1769 was identified to be the most potential hit. Docking study showed that E570-1769 bound to NA with a binding energy of -10.3 kcal/mol. Moreover, in silico ADME/T studies demonstrated the druggability of E570-1769 was quite well. Furthermore, in vitro assay demonstrated that E570-1769 inhibited the wild-type and H274Y-muatated NAs with IC₅₀ values of 72.6 μM and 229 μM, respectively. Additionally, molecular dynamic (MD) simulation studies were performed to gain a deep insight into the binding modes of E570-1769 in complex with NA. While less potent than oseltamivir, the novel structure of E570-1769 and promising ADME/T properties indicates it as a promising lead for future research.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3535-3546"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Drug Repurposing Screening Targeting Profibrotic Cytokine in Acute Respiratory Distress Syndrome.","authors":"Yong Mao, Wei Xu, Li Chen, Handi Liao","doi":"10.1007/s12013-025-01762-x","DOIUrl":"10.1007/s12013-025-01762-x","url":null,"abstract":"<p><p>Acute Respiratory Distress Syndrome (ARDS) is a severe lung disease with a high fatality rate and few treatment options. Targeting certain signalling pathways, notably the Transforming Growth Factor-beta (TGF-beta) signalling pathway, has emerged as a promising option for ARDS therapy. We identified TGF-beta Receptor 1 (TGFBR1) as a major target for ARDS treatment using the STRING and KEGG databases and validated TGFBR1's critical function in the TGF-beta signalling pathway, which is important in ARDS pathogenesis. To find prospective TGFBR1 inhibitors, we selected two FDA-approved medicines, Galunisertib and Vactosertib, which are established pharmacological profiles in cancer and fibrotic illnesses. Furthermore, the SwissSimilarity platform's ligand-based virtual screening revealed structurally related drugs in the DrugBank and ChEMBL databases. Among these, seven candidates were selected for further consideration. Molecular docking experiments found that DB08387 and CHEMBL14297639 had the strongest affinity for TGFBR1, creating strong hydrogen bonds at key sites. These findings point to their potential as TGFBR1 inhibitors in ARDS treatment. The pharmacokinetic screening revealed that most of the chosen compounds had favourable ADME features, with CHEMBL14297639 standing out for its low gastrointestinal absorption and limited cytochrome P450 inhibition. This study demonstrates the possibility of targeting TGFBR1 with Galunisertib, Vactosertib, and other prospective ARDS treatments. The findings lay the groundwork for additional experimental validation and the development of innovative therapeutics aimed at reducing ARDS severity.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3877-3888"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Liraglutide, a GLP-1 Receptor Agonist, on High Glucose-Induced Inflammation, Apoptosis, Oxidative Stress, and NLRP3 Signaling.","authors":"Mustafa Gokce, Dilek Ozturk Civelek, Aylin Vidin Sen, Eray Metin Guler, Erkan Civelek, Birsel Sonmez Uydes Dogan, F Ilkay Alp Yildirim","doi":"10.1007/s12013-025-01742-1","DOIUrl":"10.1007/s12013-025-01742-1","url":null,"abstract":"<p><p>Diabetes-related endothelial dysfunction, alteration in cell signaling, increased oxidative stress and activation of pro-inflammatory processes are the main causes of diabetes-related vascular complications. Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) play a crucial role in regulating glucose homeostasis, insulin secretion, and reducing inflammation. GLP-1R agonists have been explored for their potential in mitigating diabetes-related vascular dysfunction. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key protein complex in immune response, activates caspase-1 and promotes proinflammatory cytokine secretion. High glucose levels activate NLRP3 in macrophages via reactive oxygen species and mitochondrial dysfunction. This study aims to investigate the effects of GLP-1 receptor agonist, Liraglutide, on cell proliferation, inflammation, oxidative stress and NLRP3-related signaling pathways in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cell (HCAEC) cultures. HUVEC and HCAEC were incubated with Liraglutide (10 and 100 nM, 48 h) either in normoglycemic (5.5 mM) or hyperglycemic (25 mM) condition. Cell proliferation, oxidative stress, mRNA and protein expressions of ASC, caspase-1, NLRP3 which are. components of NLRP3 inflammasome, were determined. Our results showed that, Liraglutide significantly reduced hyperglycemia-induced oxidative stress, mRNA and protein expressions of NLRP3 inflammasome and proinflammatory cytokine levels, as well as cell membrane damage in HUVEC and HCAEC. Our results indicate that Liraglutide may have the potential on preventing hyperglycemia-induced cellular damage by reducing inflammation and immune response activation both in human venous and arterial endothelial cells.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3619-3632"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Expression Profiling Identifies CAV1, CD44, and TFRC as Potential Diagnostic Markers and Therapeutic Targets for Multiple Myeloma.","authors":"Awais Ali, Syed Luqman Ali, Waseef Ullah, Asifullah Khan","doi":"10.1007/s12013-025-01743-0","DOIUrl":"10.1007/s12013-025-01743-0","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a highly malignant hematological tumor with a low overall survival rate, making the identification of innovative prognostic markers essential due to its complex and heterogeneous nature. Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, is now recognized as crucial in tumor development and progression. Consequently, ferroptosis-related genes (FRGs) are emerging as promising therapeutic targets and prognostic indicators. However, the specific roles and predictive value of FRGs in MM still remain unclear. The current study was therefore conceived to examine the possible involvement of FRGs in MM. FRGs data was obtained from the FerrDb resource. The datasets GSE133346 and GSE166122, sourced from the Gene Expression Omnibus (GEO), provided gene expression data for both healthy and MM individuals. The differentially expressed-FRGs (DE-FRGs) were identified using the limma and DESeq2 packages in R. Functional pathways were analyzed through Gene Ontology (GO) and KEGG enrichment analyses. The miRWalk database was used for miRNA association and enrichment analysis with hub genes. Prognosis-related genes were evaluated using Kaplan-Meier survival analyses. We identified 1400 differentially expressed genes and cross-referenced them with FRGs, ultimately selecting 17 as DE-FRGs or hub genes. GO analysis revealed that the primary enriched functions of these hub genes are sister chromatid segregation, condensed chromosome centromeric region, C-C chemokine receptor activity, and C-C chemokine binding. KEGG pathway analysis showed that these overlapped genes were enriched in several pathways, including cell cycle, viral protein interaction with cytokine and cytokine receptor, as well as breast and prostate cancers involved pathways. Furthermore, significant enrichment was observed in glycolysis, gluconeogenesis, and the citrate cycle pathways based on miRNAs association with the candidate genes. The CAV1, CD44, TFRC, DPP4, and GJA1 are identified as top five significant hub DE-FRGs based on protein-protein interaction (PPI) analysis from multiple resources. Survival analysis eventually identified CAV1, CD44, and TFRC as the top-ranked DE-FRGs associated with overall survival, underscoring their crucial role in MM. This study identifies CAV1, CD44, and TFRC as key FRGs associated with the prognosis of MM, suggesting their potential as valuable prognostic markers and therapeutic targets to improve patient outcomes.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3633-3650"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphine Contributes to Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells by Blocking COX-2 Methylation via Regulating the miR-23a-3p/DNMT3A Feedback.","authors":"Jian Cui, Nina Ma, Xiaohui Li, Xuexin Chen, Junxia Zhang, Wenjuan Zhang, Hong Li","doi":"10.1007/s12013-025-01749-8","DOIUrl":"10.1007/s12013-025-01749-8","url":null,"abstract":"<p><p>To investigate the effects and mechanisms of morphine on epithelial-mesenchymal transformation (EMT) in triple-negative breast cancer (TNBC). The levels of miR-23a-3p, DNMT3A, and COX-2 in tumor tissues from metastatic TNBC patients treated with morphine were assessed using qRT-PCR. Functional assays assessed morphine's impact on TNBC cell malignancy. Dual luciferase reporter and RNA pull-down assays investigated the interaction between miR-23a-3p and DNMT3A. miR-23a-3p inhibitor and DNMT3A siRNA were transfected into TNBC cells. Protein expression was analyzed by Western blot. Methylation status of miR-23a-3p and COX-2 was assessed via methylation-specific PCR. Rescue experiments were performed to research whether morphine modulates EMT in TNBC through COX-2 methylation regulation via the miR-23a-3p/DNMT3A feedback loop. The effects of morphine on TNBC in nude mice xenotransplantation were studied. In metastatic TNBC patients treated with morphine, miR-23a-3p and COX-2 expression were elevated, and DNMT3A levels were reduced. In TNBC cells, morphine enhanced migration, invasion, and EMT, and suppressed apoptosis. It upregulated miR-23a-3p and COX-2; downregulated DNMT3A; and inhibited methylation of miR-23a-3p and COX-2. miR-23a-3p directly inhibited DNMT3A expression. In morphine-treated TNBC cells, silencing DNMT3A reduced methylation of miR-23a-3p and COX-2. miR-23a-3p inhibitor suppressed migration, invasion, and EMT, and promoted apoptosis; however, these effects were reversed by DNMT3A silencing. In vivo, morphine promoted tumor EMT and metastasis in TNBC; reduced miR-23a-3p and COX-2 methylation; and decreased DNMT3A expression. Morphine accelerated EMT in TNBC by inhibiting COX-2 methylation through the miR-23a-3p/DNMT3A loop.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3717-3729"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANO6 Targets TMEM30A to Regulate Endoplasmic Reticulum Stress-Induced Lipid Peroxidation and Ferroptosis in Alzheimer's Cells.","authors":"Ying Wang, Penghui Li, Yonghan Liang, Dandan Wang","doi":"10.1007/s12013-025-01748-9","DOIUrl":"10.1007/s12013-025-01748-9","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, and the role of ANO6 in its progression remains largely unexplored. GSE118553 database was analyzed for ANO6 expression in AD. A total of 1 μmol/L Aβ1-42 treated SH-SY5Y cells were constructed as a cell model of AD. qRT-PCR and ELISA were used to detect the expression of ANO6, GPX4, ATF6, GRP78, IREIα expression and lipid peroxidation level. Endoplasmic reticulum(ER) stress was induced by using clindamycin and lipid peroxidation indicators were detected. ANO6 was concurrently regulated in ER stress induced by clindamycin treatment. The STRING-DB database was utilized to predict potential target molecules of ANO6, while Western blot analysis was conducted to detect the expression levels of TMEM30A and evaluate the impact of ANO6-targeted TMEM30A on the protein levels within the PERK-eIF2α-ATF4-CHOP pathway. ANO6 was highly expressed in AD model, Aβ1-42 induced ANO6 enrichment in SH-SY5Y cells. ANO6 interference increased the proliferation level of AD model cells, decreased the levels of GPX4, an indicator of ferroptosis, and lipid peroxidation, and down-regulated the expression of the ER stress-related proteins ATF6, GRP78, and IREIα. Clotrimazole-induced ER stress in AD model cells showed elevated expression of ANO6. ANO6 could target and inhibit TMEM30A to affect PERK-eIF2α-ATF4-CHOP pathway activity, regulate ER stress-dependent ferroptosis, and reduce neuronal loss injury. ANO6 can target inhibition of TMEM30A affecting PERK- IF2α- ATF4- CHOP pathway activity, modulate ER stress-dependent ferroptosis-induced AD progression to reduce neuronal loss injury.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3707-3715"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Difference Analysis of MiRNA Expression Profiles in Aged Female Rat Adipose Tissue Regulated by HIIT and MICT.","authors":"Pinshi Ni, Yingmin Su, Zhuangzhi Wang, Jianmei Cui, Peng Lu, Fanghui Li","doi":"10.1007/s12013-025-01757-8","DOIUrl":"10.1007/s12013-025-01757-8","url":null,"abstract":"<p><p>Aging is frequently associated with dysregulated lipid metabolism, while exercise may improve metabolic health, a process in which microRNAs (miRNAs) play a pivotal regulatory role. However, the specific modulation of miRNA expression profiles by different exercise modalities remains poorly characterized. This study aimed to investigate adipose tissue miRNA profiles in aged rats following high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Eighteen-month-old female rats were divided into three groups (n = 12/group): sedentary (SED), MICT, and HIIT. After 8 weeks of exercise interventions, metabolic outcomes were assessed using Oil Red O staining to quantify intracellular lipid deposition, alongside Western blotting, immunofluorescence, and RT-qPCR to evaluate mRNA and protein expression of adipose tissue markers. Additionally, miRNA sequencing was performed on visceral adipose tissue to identify differentially expressed miRNAs (DEMs), followed by bioinformatic prediction of miRNA-mRNA interactions. Key findings revealed that the HIIT group exhibited more pronounced metabolic benefits compared to MICT, including reduced lipid accumulation (fewer Oil Red O-positive adipocytes) and upregulated expression of lipolytic and autophagy-related proteins (ATGL, HSL, PPAR-γ, ATG3, ATG5, ATG7, ATG12, and ATG16L). miRNA sequencing demonstrated greater divergence in expression profiles between HIIT and SED groups than between MICT and SED groups. KEGG pathway analysis highlighted significant enrichment in the MAPK, PI3K-Akt, and Rap1 signaling pathways. Furthermore, 11 DEMs (e.g., miR-34a, miR-146a) were identified as potential regulators of adipose aging, with hub genes including Shc1, Grb2, Itgb1, Ptpn11, Mapk14, Fyn, Plcg1, Sos1, and Actg1. In conclusion, HIIT significantly ameliorates age-related adipocyte inflammation and metabolic dysfunction. Exercise-induced miRNA reprogramming may alleviate the functional decline of aged adipose tissue, and HIIT-induced miRNA reprogramming is more abundant. The miRNA sequencing data pinpoint critical regulatory genes and pathways, providing novel insights into the molecular mechanisms by which exercise counteracts metabolic abnormalities in aged adipose tissue.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3833-3844"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Mechanisms Driving the Selective Efficacy of Oxamniquine against Schistosoma mansoni and Schistosoma japonicum.","authors":"Kehinde F Paul-Odeniran, Emmanuel A Iwuchukwu, Paul O Odeniran","doi":"10.1007/s12013-025-01756-9","DOIUrl":"10.1007/s12013-025-01756-9","url":null,"abstract":"<p><p>Oxamniquine (OXA) exhibits selective efficacy against different Schistosoma species, with the highest activity observed in Schistosoma mansoni sulfotransferase (SmSULT) and the lowest in Schistosoma japonicum sulfotransferase (SjSULT). This study utilises advanced atomistic and molecular simulations to elucidate the structural dynamics induced by OXA binding to SmSULT and SjSULT, aiming to unravel the underpinnings of this selective efficacy. Binding free energy (BFE) analyses revealed a markedly higher affinity of OXA for SmSULT (-48.04 kcal/mol) compared to wtSjSULT (-22.84 kcal/mol), with a significant restoration of binding affinity (-39.23 kcal/mol) observed in SjSULT following the mutation of Val139 to Gly139. Comprehensive conformational assessments highlighted that SmSULT-OXA achieves its superior efficacy by stabilising the protein structure, in stark contrast to the erratic conformational behaviour of wild-type SjSULT. Notably, this erratic behaviour is ameliorated upon mutation, leading to a restoration of OXA's efficacy in SjSULT. These insights elucidate the structural mechanisms underpinning OXA's selective efficacy and provide valuable perspectives on its targeted action against Schistosoma spp.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3815-3831"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}