International Journal of Molecular Sciences最新文献

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Molecular Interplay Between PTEN, ARID1A, PD-L1, and MMR in Asian Ovarian Clear Cell Carcinoma: Implications for Immunotherapy Response and Patient Stratification. 亚洲卵巢透明细胞癌中PTEN、ARID1A、PD-L1和MMR之间的分子相互作用:对免疫治疗反应和患者分层的影响
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104915
Chen-Hsuan Wu, Hao Lin, Yu-Che Ou, Hung-Chun Fu, Ming-Yu Yang, Chao-Cheng Huang
{"title":"Molecular Interplay Between PTEN, ARID1A, PD-L1, and MMR in Asian Ovarian Clear Cell Carcinoma: Implications for Immunotherapy Response and Patient Stratification.","authors":"Chen-Hsuan Wu, Hao Lin, Yu-Che Ou, Hung-Chun Fu, Ming-Yu Yang, Chao-Cheng Huang","doi":"10.3390/ijms26104915","DOIUrl":"10.3390/ijms26104915","url":null,"abstract":"<p><p>Ovarian clear cell carcinoma (OCCC) represents a distinct histological subtype with a high prevalence in Asian populations and poor chemotherapy response. This study investigated molecular interactions between phosphatase and tensin homolog (PTEN), AT-rich interactive domain 1A (ARID1A), programmed death-ligand 1 (PD-L1), and mismatch repair (MMR) proteins in Asian patients with OCCC. Immunohistochemical analysis was performed on tissue microarrays from 69 OCCC cases. The expression of PTEN, ARID1A, PD-L1, and four MMR proteins was evaluated alongside clinical data. A high prevalence of PTEN loss (78.3%) and ARID1A deficiency (48.8%), with PD-L1 expression in 26.1% and MMR deficiency in 10.1% of cases, was observed. All PD-L1-positive tumors demonstrated concurrent PTEN loss (<i>p</i> = 0.007). MMR deficiency was significantly associated with ARID1A loss (<i>p</i> = 0.049). PTEN loss correlated with worse progression-free survival (PFS) in early-stage disease (<i>p</i> = 0.039). PTEN and ARID1A alterations represent early pathogenic events in Asian OCCC, with PTEN loss significantly impacting PFS in early-stage disease. The correlation between PTEN loss and PD-L1 expression, alongside ARID1A-MMR deficiency association, provides insights into OCCC's immunological landscape and therapeutic vulnerabilities.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glycomics and Glycoproteomics Reveal Distinct Oligomannose Carriers Across Bladder Cancer Stages. 糖组学和糖蛋白组学揭示膀胱癌分期不同的寡甘露糖携带者。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104891
Marta Relvas-Santos, Dylan Ferreira, Andreia Brandão, Luis Pedro Afonso, Lúcio Lara Santos, André M N Silva, José Alexandre Ferreira
{"title":"Glycomics and Glycoproteomics Reveal Distinct Oligomannose Carriers Across Bladder Cancer Stages.","authors":"Marta Relvas-Santos, Dylan Ferreira, Andreia Brandão, Luis Pedro Afonso, Lúcio Lara Santos, André M N Silva, José Alexandre Ferreira","doi":"10.3390/ijms26104891","DOIUrl":"10.3390/ijms26104891","url":null,"abstract":"<p><p>Aberrant glycosylation is a hallmark of cancer, offering opportunities to enhance clinical decision-making and enable precise targeting of cancer cells. Nevertheless, alterations in the bladder urothelial carcinoma (BLCA) <i>N</i>-glycome remain poorly characterized. Here, we used in situ <i>N</i>-deglycosylation and mass spectrometry, revealing a marked enrichment of oligomannose-type <i>N</i>-glycans in non-invasive Ta tumors, which diminished with disease progression. A complementary analysis of The Cancer Genome Atlas (TCGA) transcriptomic data revealed downregulation of the key mannosidases in BLCA, suggesting a mechanistic basis for oligomannose accumulation, though this requires further validation. Then, targeted glycoproteomic profiling identified potential stage-specific carriers of oligomannoses. Exploratory functional annotation suggests stage-dependent differences among detected glycoproteins, ranging from metabolic regulation in Ta tumors to oxidative stress adaptation in muscle-invasive disease, highlighting glycosylation's contribution to tumor progression. Furthermore, myeloperoxidase (MPO) was enriched in more aggressive stages. Spatial validation confirmed MPO overexpression in tumor-infiltrating immune cells and its correlation with oligomannose content. Importantly, high MPO expression combined with low mannosidase levels was linked to poor survival, suggesting biological relevance. This study suggests a dynamic, stage-specific <i>N</i>-glycome in BLCA and identifies oligomannose-bearing glycoproteins as exploratory leads for biomarker and therapeutic target discovery, providing a <i>N</i>-glycomic resource for further investigation towards glycan-based precision oncology.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acetazolamide-Loaded Nanoparticle Based on Modified Hyaluronic Acid as Delivery System to Target Carbonic Anhydrases in Escherichia coli. 基于修饰透明质酸的载乙酰唑胺纳米颗粒对大肠杆菌碳酸酐酶的递送。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104908
Valentina Verdoliva, Viviana De Luca, Claudiu T Supuran, Stefania De Luca, Clemente Capasso
{"title":"Acetazolamide-Loaded Nanoparticle Based on Modified Hyaluronic Acid as Delivery System to Target Carbonic Anhydrases in <i>Escherichia coli</i>.","authors":"Valentina Verdoliva, Viviana De Luca, Claudiu T Supuran, Stefania De Luca, Clemente Capasso","doi":"10.3390/ijms26104908","DOIUrl":"10.3390/ijms26104908","url":null,"abstract":"<p><p>Acetazolamide (AZA) is a validated carbonic anhydrase inhibitor (CAI) that has the potential for use in various therapeutic applications. Herein, we report a novel AZA-loaded biodegradable nanodelivery system that was proven to enhance the antibacterial efficacy of the drug against Gram-negative bacteria, such as <i>Escherichia coli.</i> Carbonic anhydrases (CA, EC 4.2.1.1) in <i>E. coli</i> play a crucial role in bacterial metabolism and CO<sub>2</sub>/HCO<sub>3</sub><sup>-</sup> balance; therefore, they represent a suitable target for antimicrobial strategies. The nanoparticles were obtained using a green synthetic protocol that allowed conjugation of a natural fatty acid to hyaluronic acid (HA) under solvent-free conditions. Full characterization of the micellar aggregates was performed (diameter of the micelles, zeta potential, and drug release study). In vitro studies demonstrated that AZA loaded in HA-based nanoparticles significantly inhibited <i>E. coli</i> growth at concentrations as low as 0.5 µg/mL, whereas higher concentrations of free AZA were required, as previously reported. Additionally, encapsulated AZA disrupted glucose consumption in <i>E. coli</i>, indicating its profound impact on bacterial metabolism. These findings suggest that the HA-palmitate nanoparticle not only enhances the delivery and efficacy of AZA but also offers a strategy to affect bacterial metabolism.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12111950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deciphering the Causes of IbfA-Mediated Abortive Infection in the P22-like Phage UAB_Phi20. 解读ibfa介导的p22样噬菌体UAB_Phi20流产感染的原因。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104918
Júlia López-Pérez, Pilar Cortés, Susana Campoy, Ivan Erill, Montserrat Llagostera
{"title":"Deciphering the Causes of IbfA-Mediated Abortive Infection in the P22-like Phage UAB_Phi20.","authors":"Júlia López-Pérez, Pilar Cortés, Susana Campoy, Ivan Erill, Montserrat Llagostera","doi":"10.3390/ijms26104918","DOIUrl":"10.3390/ijms26104918","url":null,"abstract":"<p><p>The study of bacterial defense mechanisms against phages is becoming increasingly relevant due to their impact on the effectiveness of phage therapy. Employing a multifaceted approach that combines bioinformatics, molecular microbiology, TEM microscopy, and conventional microbiology techniques, here, we identify the <i>ibfA</i> gene as a novel defense factor targeting the virulent phage UAB_Phi20, acquired by <i>Salmonella</i> Typhimurium through lateral transfer on the IncI1α conjugative plasmid pUA1135 after oral phage therapy in broilers. IbfA, a two-domain protein containing ATPase and TOPRIM domains, significantly reduces UAB_Phi20 productivity, as indicated by decreased EOP, ECOI, and a diminished burst size, potentially reducing cellular viability without causing observable lysis. Our results indicate that IbfA enhances the transcription of early genes, including the antirepressor <i>ant</i>, which inhibits the C2 repressor of the lytic cycle. This may cause an imbalance in Cro/C2 concentration, leading to the observed reduction in the transcription of late genes encoding structural and cellular lysis proteins, and resulting in the abortion of UAB_Phi20 infection.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12111858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Challenges of Studying Amelogenesis in Gene-Targeted Mouse Models. 在基因靶向小鼠模型中研究变形发生的挑战。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104905
Charles E Smith, John D Bartlett, James P Simmer, Jan C-C Hu
{"title":"Challenges of Studying Amelogenesis in Gene-Targeted Mouse Models.","authors":"Charles E Smith, John D Bartlett, James P Simmer, Jan C-C Hu","doi":"10.3390/ijms26104905","DOIUrl":"10.3390/ijms26104905","url":null,"abstract":"<p><p>Research on how a stratified oral epithelium gained the capability to create the hardest hydroxyapatite-based mineralized tissue produced biologically to protect the surfaces of teeth has been ongoing for at least 175 years. Many advances have been made in unraveling some of the key factors that allowed the innermost undifferentiated epithelial cells sitting on a skin-type basement membrane to transform into highly polarized cells capable of forming and controlling the mineralization of the extracellular organic matrix that becomes enamel. Genetic manipulation of mice has proven to be a useful approach for studying specific events in the amelogenesis developmental sequence but there have been pitfalls in interpreting loss of function data caused in part by conflicting literature, technical problems in tissue preservation, and the total amount of time spent on tooth development between different species that have led to equivocal conclusions. This critical review attempts to discuss some of these issues and highlight the challenges of characterizing amelogenesis in gene-targeted mouse models.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic-Thermodynamic Phase Synchronization: Maxwell's Demon-like Regulation of Cell Fate Transition. 基因组-热力学阶段同步:麦克斯韦对细胞命运转变的魔鬼般的调控。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104911
Masa Tsuchiya, Kenichi Yoshikawa, Alessandro Giuliani
{"title":"Genomic-Thermodynamic Phase Synchronization: Maxwell's Demon-like Regulation of Cell Fate Transition.","authors":"Masa Tsuchiya, Kenichi Yoshikawa, Alessandro Giuliani","doi":"10.3390/ijms26104911","DOIUrl":"10.3390/ijms26104911","url":null,"abstract":"<p><p>Dynamic criticality-the balance between order and chaos-is fundamental to genome regulation and cellular transitions. In this study, we investigate the distinct behaviors of gene expression dynamics in MCF-7 breast cancer cells under two stimuli: heregulin (HRG), which promotes cell fate transitions, and epidermal growth factor (EGF), which binds to the same receptor but fails to induce cell-fate changes. We model the system as an open, nonequilibrium thermodynamic system and introduce a convergence-based approach for the robust estimation of information-thermodynamic metrics. Our analysis reveals that the Shannon entropy of the critical point (CP) dynamically synchronizes with the entropy of the rest of the whole expression system (WES), reflecting coordinated transitions between ordered and disordered phases. This phase synchronization is driven by net mutual information scaling with CP entropy dynamics, demonstrating how the CP governs genome-wide coherence. Furthermore, higher-order mutual information emerges as a defining feature of the nonlinear gene expression network, capturing collective effects beyond simple pairwise interactions. By achieving thermodynamic phase synchronization, the CP orchestrates the entire expression system. Under HRG stimulation, the CP becomes active, functioning as a Maxwell's demon with dynamic, rewritable chromatin memory to guide a critical transition in cell fate. In contrast, under EGF stimulation, the CP remains inactive in this strategic role, passively facilitating a non-critical transition. These findings establish a biophysical framework for cell fate determination, paving the way for innovative approaches in cancer research and stem cell therapy.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions. 运动神经元疾病的遗传基础:见解、临床管理和未来方向。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104904
Apostolos Antonakoudis, Stella Aikaterini Kyriakoudi, Despoina Chatzi, Iasonas Dermitzakis, Sofia Gargani, Soultana Meditskou, Maria Eleni Manthou, Paschalis Theotokis
{"title":"Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.","authors":"Apostolos Antonakoudis, Stella Aikaterini Kyriakoudi, Despoina Chatzi, Iasonas Dermitzakis, Sofia Gargani, Soultana Meditskou, Maria Eleni Manthou, Paschalis Theotokis","doi":"10.3390/ijms26104904","DOIUrl":"10.3390/ijms26104904","url":null,"abstract":"<p><p>Motor neuron diseases (MNDs) are a heterogeneous group of neurodegenerative disorders characterized by the progressive loss of motor neurons, resulting in debilitating physical decline. Advances in genetics have revolutionized the understanding of MNDs, elucidating critical genes such as <i>SOD1</i>, <i>TARDBP</i>, <i>FUS</i>, and <i>C9orf72</i>, which are implicated in their pathogenesis. Despite these breakthroughs, significant gaps persist in understanding the interplay between genetic and environmental factors, the role of rare variants, and epigenetic contributions. This review synthesizes current knowledge on the genetic landscape of MNDs, highlights challenges in linking genotype to phenotype, and discusses the promise of precision medicine approaches. Emphasis is placed on emerging strategies, such as gene therapy and targeted molecular interventions, offering hope for personalized treatments. Addressing these challenges is imperative to harness the full potential of genomics for improving outcomes in MNDs.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Machine Learning on Toxicogenomic Data Reveals a Strong Association Between the Induction of Drug-Metabolizing Enzymes and Centrilobular Hepatocyte Hypertrophy in Rats. 基于毒物基因组学数据的机器学习揭示了药物代谢酶的诱导与大鼠小叶中心肝细胞肥大之间的密切联系。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104886
Kazuki Ikoma, Takuomi Hosaka, Akira Ooka, Ryota Shizu, Kouichi Yoshinari
{"title":"Machine Learning on Toxicogenomic Data Reveals a Strong Association Between the Induction of Drug-Metabolizing Enzymes and Centrilobular Hepatocyte Hypertrophy in Rats.","authors":"Kazuki Ikoma, Takuomi Hosaka, Akira Ooka, Ryota Shizu, Kouichi Yoshinari","doi":"10.3390/ijms26104886","DOIUrl":"10.3390/ijms26104886","url":null,"abstract":"<p><p>Centrilobular hepatocyte hypertrophy is frequently observed in animal studies for chemical safety assessment. Although its toxicological significance and precise mechanism remain unknown, it is considered an adaptive response resulting from the induction of drug-metabolizing enzymes (DMEs). This study aimed to elucidate the association between centrilobular hepatocyte hypertrophy and DME induction using machine learning on toxicogenomic data. Utilizing publicly available gene expression data and pathological findings from rat livers of 134 compounds, we developed six different types of machine learning models to predict the occurrence of centrilobular hepatocyte hypertrophy based on gene expression data as explanatory variables. Among these, a LightGBM-based model demonstrated the best performance with an accuracy of approximately 0.9. With this model, we assessed each gene's contribution to predicting centrilobular hepatocyte hypertrophy using mean absolute SHAP values. The results revealed that <i>Cyp2b1</i> had an extremely significant contribution, while other DME genes also displayed positive contributions. Additionally, enrichment analysis of the top 100 genes based on mean absolute SHAP values identified \"Metabolism of xenobiotics by cytochrome P450\" as the most significantly enriched term. In conclusion, the current results suggest that the induction of multiple DMEs, including CYP2B1, is crucial for the development of centrilobular hepatocyte hypertrophy.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Femtosecond Laser-Engineered β-TCP Scaffolds: A Comparative Study of Green-Synthesized AgNPs vs. Ion Doping Against S. aureus for Bone Regeneration. 飞秒激光工程β-TCP支架:绿色合成AgNPs与离子掺杂抗金黄色葡萄球菌骨再生的比较研究。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-20 DOI: 10.3390/ijms26104888
Marco Oliveira, Liliya Angelova, Georgi Avdeev, Liliana Grenho, Maria Helena Fernandes, Albena Daskalova
{"title":"Femtosecond Laser-Engineered β-TCP Scaffolds: A Comparative Study of Green-Synthesized AgNPs vs. Ion Doping Against <i>S. aureus</i> for Bone Regeneration.","authors":"Marco Oliveira, Liliya Angelova, Georgi Avdeev, Liliana Grenho, Maria Helena Fernandes, Albena Daskalova","doi":"10.3390/ijms26104888","DOIUrl":"10.3390/ijms26104888","url":null,"abstract":"<p><p>Implant-associated infections, particularly those linked to <i>Staphylococcus aureus</i> (<i>S. aureus</i>), continue to compromise the clinical success of β-tricalcium phosphate (β-TCP) implants despite their excellent biocompatibility and osteoconductivity. This investigation aims to tackle these challenges by integrating femtosecond (fs)-laser surface processing with two complementary strategies: ion doping and functionalization with green-synthesized silver nanoparticles (AgNPs). AgNPs were produced via fs-laser photoreduction using green tea leaf extract (GTLE), noted for its anti-inflammatory and antioxidant properties. Fs-laser processing was applied to modify β-TCP scaffolds by systematically varying scanning velocities, fluences, and patterns. Lower scanning velocities generated organized nanostructures with enhanced roughness and wettability, as confirmed by scanning electron microscopy (SEM), optical profilometry, and contact angle measurements, whereas higher laser energies induced significant phase transitions between hydroxyapatite (HA) and α-tricalcium phosphate (α-TCP), as revealed by X-ray diffraction (XRD). AgNP-functionalized scaffolds demonstrated markedly superior antibacterial activity against <i>S. aureus</i> compared to the ion-doped variants, attributed to the synergistic interplay of nanostructure-mediated surface disruption and AgNP-induced bactericidal mechanisms. Although ion-doped scaffolds exhibited limited direct antibacterial effects, they showed concentration-dependent activity in indirect assays, likely due to controlled ion release. Both strategies promoted osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) under defined conditions, albeit with transient cytotoxicity at higher fluences and excessive ion doping. Overall, this approach holds promise for markedly improving antibacterial efficacy and osteogenic compatibility, potentially transforming bone regeneration therapies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Black Soldier Fly Larvae Oil on Immunometabolic Processes. 黑虻幼虫油对免疫代谢过程的影响。
IF 5.6 2区 生物学
International Journal of Molecular Sciences Pub Date : 2025-05-19 DOI: 10.3390/ijms26104855
Hadas Inbart Richter, Ofer Gover, Amit Hamburg, Keren Bendalak, Tamar Ziv, Betty Schwartz
{"title":"Impact of Black Soldier Fly Larvae Oil on Immunometabolic Processes.","authors":"Hadas Inbart Richter, Ofer Gover, Amit Hamburg, Keren Bendalak, Tamar Ziv, Betty Schwartz","doi":"10.3390/ijms26104855","DOIUrl":"10.3390/ijms26104855","url":null,"abstract":"<p><p>The oil extract derived from black soldier fly (<i>Hermetia illucens</i>) larvae (BSFL) is characterized by a distinctive fatty acid composition and bioactive compounds with demonstrated anti-inflammatory properties, as shown in our previous work. The present study aims to mechanistically explore the immunomodulatory effects of a saponified form of BSFL oil (MBSFL) and its potential interaction with metabolic signaling pathways. Using Pam3CSK4-polarized M1 primary human peripheral blood mononuclear cells (PBMCs), we demonstrate that MBSFL phenotypically suppressed the secretion of pro-inflammatory cytokines TNFα, IL-6, IL-17, and GM-CSF (<i>p</i> < 0.01) without altering anti-inflammatory cytokine levels (TGFβ1, IL-13, and IL-4). A phosphoproteomic analysis of Pam3CSK4-stimulated THP-1 macrophages revealed MBSFL-mediated downregulation of CK2 and ERK kinases (<i>p</i> < 0.05), key regulators of NF-κB signaling activation. We confirmed that MBSFL directly inhibits NF-κB p65 nuclear translocation (<i>p</i> < 0.05), using both immunofluorescence staining and a western blot analysis of nuclear and cytoplasmic fractions. In the context of metabolism, using a luciferase reporter assay, we demonstrate that MBSFL functions as a weak agonist of PPARγ and PPARδ (<i>p</i> < 0.05), which are nuclear receptors involved in lipid metabolism and immune regulation. However, subsequent immunoblotting revealed a macrophage polarization-dependent regulation: MBSFL upregulated PPARγ in M0 macrophages but did not prevent its suppression upon Pam3CSK4 stimulation, whereas it specifically enhanced PPARδ expression during M1 polarization (<i>p</i> < 0.05). This study provides novel experimental evidence supporting our hypothesis of MBSFL's role in immunometabolism. We demonstrate for the first time that MBSFL acts as a dual regulator by suppressing NF-κB-mediated inflammation while promoting PPARδ activity-an inverse relationship with potential relevance to immunometabolic disorders.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144158808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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