Biochemistry and Biophysics Reports最新文献

{"title":"Comprehensive transcriptomic analysis of hepatocellular Carcinoma: Uncovering shared and unique molecular signatures across diverse etiologies","authors":"Babak Khorsand ,&nbsp;Nazanin Naderi ,&nbsp;Seyedeh Sara Karimian ,&nbsp;Maedeh Mohaghegh ,&nbsp;Alireza Aghaahmadi ,&nbsp;Seyedeh Negin Hadisadegh ,&nbsp;Mina Owrang ,&nbsp;Hamidreza Houri","doi":"10.1016/j.bbrep.2025.102123","DOIUrl":"10.1016/j.bbrep.2025.102123","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, often diagnosed at advanced stages where treatment options are limited. This study undertakes a comprehensive meta-analysis of gene expression profiles from 19 independent datasets sourced from the Gene Expression Omnibus (GEO), encompassing a diverse range of HCC etiologies, including HBV and HCV infections, cirrhosis, and normal liver comparisons. Our analysis identified 125 genes consistently altered across all datasets (e.g., <em>CYP2C9</em>, <em>SLC22A1</em>, <em>RDH5</em>) that represent a pan-etiology HCC signature, implicating retinol metabolism and solute transport as key pathways in HCC pathogenesis. Notably, 14 HBV-specific differentially expressed genes (DEGs) (e.g., <em>ABCA8</em>, <em>GADD45B</em>) and 221 HCV-specific DEGs (e.g., <em>CDK1</em>, <em>CCNB1</em>) were identified, highlighting etiology-specific molecular signatures. Protein-protein interaction (PPI) networks revealed central hubs (e.g., CDK1, CCNE1, TYMS) involved in cell cycle dysregulation and metabolic reprogramming (Warburg effect). These findings provide a robust molecular framework for HCC subtyping and prioritize novel biomarkers and therapeutic targets for further validation. This resource advances the potential for personalized HCC diagnostics and therapies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102123"},"PeriodicalIF":2.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic architecture and mechanisms shared between kidney and ureteral stones, cardiovascular diseases, and metabolic syndrome: A comprehensive GWAS analysis","authors":"Yibo Hua ,&nbsp;Zhengkai Huang ,&nbsp;Yu Yin ,&nbsp;Rijin Song ,&nbsp;Xianghu Meng","doi":"10.1016/j.bbrep.2025.102116","DOIUrl":"10.1016/j.bbrep.2025.102116","url":null,"abstract":"<div><h3>Background</h3><div>Our study aims to investigate the shared genetic architecture between kidney and ureteral stones (KUS) and cardiovascular diseases (CVDs), as well as metabolic syndrome (MetS), and explore the shared risk loci, potentially critical tissues and relevant genetic mechanisms.</div></div><div><h3>Methods</h3><div>Dependent on large-scale genome-wide association study (GWAS) summary-level data sets, we observed genetic correlations between KUS and CVDs, as well as MetS, and cross-diseases pleiotropic analysis was conducted to identify shared pleiotropic loci and genes. Furthermore, we performed functional annotation and tissue-specific analysis to detect potential relationships between complex traits. We performed heritability enrichment analysis to determine potentially critical tissues. At last, we investigate the causal effects between KUS and other traits using bidirectional Mendelian randomization (MR).</div></div><div><h3>Results</h3><div>Our findings underlined shared genetic architecture between three CVDs, two MetS and KUS. We identified 937 pleiotropic loci at the genome-wide significance level (p &lt; 5 × 10⁻⁸), 35 of which were annotated as genomic risk loci. Among them, 4 had strong evidence of colocalization (PP.H4 &gt; 0.7). In addition, a total of 163 unique pleiotropic genes (pFDR &lt;0.05) were recognized at the gene level, including FTO, NEK4, GNL3, GLT8D1, SMIM4, PBRM1 and TFAP2B. Pathway analysis illustrated the essential biological process including metabolic processes, transcriptional regulation processes, transmembrane transport of drugs, and cardiac structure development were involved in these diseases. Analysis of tissue enrichment at single nucleotide polymorphism (SNP) level and gene level indicated pleiotropic mechanisms may engage in prostate, pancreas, adipose subcutaneous, and muscle skeletal. HyPrColoc method and metabolite enrichment analysis revealed tryptophan metabolism might be a crucial shared metabolic pathway in two different diseases. At last, bidirectional MR analysis demonstrated no strong evidence of causal associations between KUS and CVDs, as well as MetS.</div></div><div><h3>Conclusions</h3><div>Our study determined shared genetic architecture between KUS and CVDs, as well as MetS, and unraveled underlying genetic mechanisms.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102116"},"PeriodicalIF":2.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The LINC01270/miR-29c-3p/LOX axis drives gastric cancer progression: Bioinformatics and experimental validation","authors":"Farideh Ghanbari Mardasi ,&nbsp;Sharareh Eskandarieh ,&nbsp;Reza Taslimi ,&nbsp;Mohammadreza Eskandarion ,&nbsp;Reza Shirkoohi ,&nbsp;Majid Kabuli","doi":"10.1016/j.bbrep.2025.102107","DOIUrl":"10.1016/j.bbrep.2025.102107","url":null,"abstract":"<div><div>Gastric cancer (GC) is the fifth most common cancer-related cause of death worldwide, characterized by high recurrence and mortality rates. Lysyl oxidase (LOX) has been implicated in GC progression, although its precise role remains unclear. Based on the competing endogenous RNA (ceRNA) hypothesis, this study aimed to identify a lncRNA–miRNA axis regulating LOX overexpression in GC. Through integrated analysis of microarray data, bioinformatics databases, and online prediction tools, we identified TUG1 and the LINC01270–miR-29c-3p axis as a novel upstream ceRNA network regulating LOX expression. These findings were validated in GC tissues and KATO III cells, where LINC01270 and LOX were significantly upregulated and inversely correlated with miR-29c-3p expression. To assess the functional relevance of this axis, we silenced LINC01270 using siRNA in KATO III cells, resulting in increased miR-29c-3p expression, decreased LOX levels, and reduced cell viability. These results suggest that LINC01270 promotes GC progression by sponging miR-29c-3p, thereby upregulating LOX, and highlight the LINC01270–miR-29c-3p–LOX axis as a potential diagnostic and therapeutic target in GC. Furthermore, LOX, LINC01270, and miR-29c-3p may serve as potential diagnostic and prognostic biomarkers in GC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102107"},"PeriodicalIF":2.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic core-shell nanoparticles for Hyperthermia: A numerical study of soft and hard core-shell magnetic materials in liver tissue based on dual phase lag model","authors":"M. Moshtagh ,&nbsp;M. Servatkhah ,&nbsp;S. Hosseini ,&nbsp;Gh Solookinejad","doi":"10.1016/j.bbrep.2025.102084","DOIUrl":"10.1016/j.bbrep.2025.102084","url":null,"abstract":"<div><div>In this article, local hyperthermia using core-shell magnetic nanoparticles based on soft and hard magnetic ferrite phases, comprising Zn _0.4Co _0.6Fe ₂O ₄ @Zn _0.4 Mn _0.6 Fe ₂O ₄, under the influence of an AC magnetic field, has been numerically investigated to simulate heat distribution and tumor destruction in liver tissue.</div><div>It is observed that the dual-phase-lag (DPL) model predicts the maximum temperature lower than both the Pennes bioheat and the single-phase-lag (SPL) model. In addition simulation of temperature distribution over time considering different core-shell nanoparticles in AC magnetic field, has been performed using DPL model. The highest temperature is related to Zn _0.4 Co _0.6 Fe ₂O₄ @Zn _0.4 Mn _0.6 Fe ₂O₄ and the lowest temperature is related to MnFe₂O₄.We have concluded that these combinations maximize the properties of magnetic nanoparticles and have higher SLP values and more power dissipation of magnetic nanoparticles compared to magnetic nanoparticles of MnFe₂O ₄, MnFe₂O₄ @ CoFe₂O₄ and CoFe₂O₄ @MnFe₂O4.</div><div>Two-dimensional temperature distribution simulation over time in liver tissue has been performed using DPL model to quantitatively investigate the tumor temperature in different locations. The results show that temperature curves is a Gaussian-like distribution. The temperature curve is symmetric around the y axis. Temperature is maximum at the center of the tumor and decreases radially outward.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102084"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promotive role of MBNL3 and PXN genes expressions with lncRNA PXN-AS1-L on gastric cancer","authors":"Mai A.H. Abouelenin ,&nbsp;Amany A. Saleh ,&nbsp;Naglaa S. Elabd ,&nbsp;Osama Elbahr ,&nbsp;Reham Ahmed Abdelaziz ,&nbsp;Mohammed G. Elhelbawy ,&nbsp;Zeinab A. Kasemy ,&nbsp;Ahmed Abdelkhalek Hussein ,&nbsp;Mona A. Abbas","doi":"10.1016/j.bbrep.2025.102117","DOIUrl":"10.1016/j.bbrep.2025.102117","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer ranks fourth in both incidence and mortality worldwide. Several genes influence its genesis and progress.</div></div><div><h3>Materials and methods</h3><div>The expression of MBNL3, PXN genes, and lncRNA PXN-AS1-L was evaluated in gastric tissue samples from 75 gastric cancer patients and 75 controls by RT-PCR.</div></div><div><h3>Results</h3><div>MBNL3, PXN, and lncRNA PXN-AS1-L expressions were considerably raised among cancerous gastric tissue than in nearby normal tissue and normal tissue from controls (p &lt; 0.001). LncRNA PXN-AS1-L and MBNL3 had the highest sensitivity (92.00 % and 90.67 %, respectively), with PXN sensitivity of 81.33 % for differentiation of the cancer tissue from adjacent normal tissue, while PXN and lncRNA PXN-AS1-L had the highest sensitivity (98.67 % and 92.00 %, respectively), with 89.33 % for MBNL3 as discriminators between gastric cancer tissue and normal tissue from controls. Between metastatic and non-metastatic patients, MBNL3 and PXN were the highest differentiating markers (sensitivity = 87.50 % and 83.33 %, respectively). MBNL3, PXN, and lncRNA PXN-AS1-L were reliable predictors of gastric cancer (p = 0.004, p = 0.009, and p = 0.001, respectively), but only MBNL3 and lncRNA PXN-AS1-L were significant predictors for mortality (p = 0.026 and p = 0.043, respectively). The elevated expressions were linked to lower overall and progression-free survival rates.</div></div><div><h3>Conclusion</h3><div>MBNL3, PXN, and lncRNA PXN-AS1-L expression levels can diagnose and predict gastric cancer and discriminate between metastatic and non-metastatic patients. The expression level of MBNL3 and lncRNA PXN-AS1-L can predict gastric cancer mortality. Higher expression of MBNL3 and PXN was linked to aggressive gastric cancer and low overall and progression-free survival rates.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102117"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule-associated protein 4 forms aggregates consisting of helical filaments","authors":"Shuto Miura,&nbsp;Eisuke Ishibashi,&nbsp;Takuto Nakamichi,&nbsp;Koji Uwai,&nbsp;Masahiro Kuragano,&nbsp;Kiyotaka Tokuraku","doi":"10.1016/j.bbrep.2025.102118","DOIUrl":"10.1016/j.bbrep.2025.102118","url":null,"abstract":"<div><div>We previously reported that microtubule-associated protein (MAP) 4 was detected in the cytoplasm as abnormal “puncta” in post-ischemic mouse cardiomyocytes. MAP4, a member of the MAP superfamily, has a repeat region consisting of multiple microtubule-binding sequences in its microtubule-binding domain (MBD), like tau. The tau forms aggregates composed of amyloid fibrils and grows into neurofibrillary tangles in neurons. Therefore, we hypothesized that MAP4 also forms amyloid fibrils in cells. Here, we observed whether MAP4 forms aggregates composed of amyloid fibrils using fluorescence microscopy and transmission electron microscopy with quantum dot (QD) nanoprobes. Since we had previously succeeded in real-time 3D imaging of tau MBD fragment aggregate formation using QD nanoprobes, we attempted to observe aggregates using human MAP4 MBD fragments under the same conditions. Fluorescence microscopy showed that 10 μM MAP4 formed aggregates at a rate similar to that of tau. Time-laps 3D imaging by confocal laser microscopy revealed that MAP4 aggregate grains were smaller in size and the deposits were thinner than tau aggregates. Transmission electron microscopy of the MAP4 aggregates revealed that they consisted of helical filaments with a width of 22.6 ± 2.8 nm and a helical pitch length of 48.2 ± 8.4 nm. The helical filaments of MAP4 were shorter in width and longer in helical pitch than those of tau. Furthermore, MAP4 aggregates did not increase the fluorescence intensity of thioflavin T (ThT), and the circular dichroism (CD) spectrum slightly differed from that of tau. These findings suggest that while MAP4 forms aggregates composed of helical filaments similar to those of tau, the structural properties of these filaments are somewhat distinct.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102118"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous Plant signals and human Health: Molecular mechanisms, ecological functions, and therapeutic Prospects","authors":"Esther Ugo Alum ,&nbsp;David Chukwu Obasi ,&nbsp;Jacinta Nnennaya Abba ,&nbsp;Ugonna Cassandra Aniokete ,&nbsp;Prince Nkemakolam Okoroh ,&nbsp;Okechukwu Paul-Chima Ugwu ,&nbsp;Daniel Ejim Uti","doi":"10.1016/j.bbrep.2025.102114","DOIUrl":"10.1016/j.bbrep.2025.102114","url":null,"abstract":"<div><div>Endogenous plant signals, including phytohormones, secondary metabolites, and volatile organic compounds, play pivotal roles in plant growth, defense, and ecological interactions. Signals are crucial in plant responses to both biotic and abiotic stressors, as well as in the biosynthesis of therapeutic compounds. Jasmonic acid, salicylic acid, and ethylene are crucial signaling molecules that regulate internal and external communication, including herbivore defense and microbial interactions. Volatile organic compounds further enable plant–plant communication and ecological resilience. Increasing evidence links these signaling pathways to the production of compounds with antioxidant, anti-inflammatory, and anticancer properties in humans, bridging plant ecology with human health. This narrative review was conducted through integrative thematic synthesis of peer-reviewed literature published between 2015 and 2025, using databases such as PubMed, Scopus, and ScienceDirect. Articles were selected based on their relevance to the molecular mechanisms, ecological roles, and therapeutic implications of endogenous plant signals. Emphasis was placed on interdisciplinary studies spanning molecular biology, pharmacology, and systems ecology. This review explores recent advancements in plant signals' molecular and ecological roles, emphasizing their importance in sustainable agriculture, drug discovery, and functional foods. Signaling networks' complexity necessitates interdisciplinary strategies involving molecular biology, systems ecology, and pharmacology, which can be harnessed through biotechnology and systems-based research for therapeutic and ecological innovations.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102114"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant PD-1 blockade induces the autophagy of immune cells: a new target for synergistic therapy of recurrent glioblastoma","authors":"Zixue Xuan ,&nbsp;Kai Wang ,&nbsp;Qingxia Zhu ,&nbsp;Ting Sun ,&nbsp;Jinying Jiang ,&nbsp;Zhongxiu Wu ,&nbsp;Shuilian Zheng ,&nbsp;Hongying Zhao","doi":"10.1016/j.bbrep.2025.102119","DOIUrl":"10.1016/j.bbrep.2025.102119","url":null,"abstract":"<div><h3>Background</h3><div>Neoadjuvant PD-1 blockade may incidentally modulate autophagy in immune cells, which could contribute to drug resistance and tumor relapse. However, the specific immune cell subsets affected by neoadjuvant PD-1 blockade in terms of autophagy remain to be fully elucidated, as well as the drugs that might influence these processes.</div></div><div><h3>Methods</h3><div>Single-cell sequencing data from tissues of recurrent glioblastoma (GBM.rec) and GBM treated with neoadjuvant PD-1 blockade (GBM.PD1) were analyzed to investigate the changes in autophagy within immune cells in the GBM.PD1 group. Subsequently, the functional characteristics of subtypes regulated by membrane proteins were explored, and potential drugs targeting key immune cell subsets mediated by these proteins were identified.</div></div><div><h3>Results</h3><div>Neoadjuvant PD-1 blockade significantly increased the proportion of lymphoid cells with elevated autophagy. This elevated autophagy level was associated with specific ligand-receptor interactions in GBM, such as HLA-DRA–CD4. Immune cell subtypes, particularly those with both lymphoid and myeloid signatures (L + M cells, APOE + cells), exhibited strong associations with autophagy. These L + M cells demonstrated significantly more T cell-related interactions in the GBM.PD1 group, with notable receptor-ligand interactions like GZMA-F2R. Furthermore, ribavirin, which targets CXCL8 and IL6, was identified as a potential drug candidate for targeting L + M cells.</div></div><div><h3>Conclusion</h3><div>L + M cells may represent critical immune components involved in autophagy induced by neoadjuvant PD-1 blockade. The interactions between HLA-DRA and CD4, as well as between GZMA and F2R, are crucial for modulating immune responses. Moreover, ribavirin, targeting CXCL8 and IL6, has the potential to enhance the efficacy of neoadjuvant PD-1 blockade.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102119"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144491895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesendodermal cells fail to contribute to heart formation following blastocyst injection","authors":"Biyi Li,&nbsp;Chulan Kwon","doi":"10.1016/j.bbrep.2025.102120","DOIUrl":"10.1016/j.bbrep.2025.102120","url":null,"abstract":"<div><div>Blastocyst complementation offers an opportunity for generating transplantable whole organs from donor sources. Pluripotent stem cells (PSCs) have traditionally served as the primary donor cells due to their ability to differentiate into any type of body cell. However, the use of PSCs raises ethical concerns, particularly regarding their uncontrollable differentiation potential to undesired cell lineages such as brain and germline cells. To address this issue, various strategies have been explored, including the use of genetically modified PSCs with restricted lineage potential or lineage-specified progenitor cells as donors. In this study, we tested whether nascent mesendodermal cells (MECs), which appear during early gastrulation, can be used as donor cells. To do this, we induced Bry-GFP⁺ MECs from mouse embryonic stem cells (ESCs) and introduced them into the blastocyst. While donor ESCs gave rise to various regions of embryos, including the heart, Bry-GFP⁺ MECs failed to contribute to the host embryos. This finding suggests that MECs, despite being specified from PSCs within a few days, lack the capacity to assimilate into the developing embryo.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102120"},"PeriodicalIF":2.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of phosphodiesterase inhibitors on platelet function","authors":"Ravi Hochuli,&nbsp;Valerie Dicenta,&nbsp;Zoi Laspa,&nbsp;Manuel Sigle,&nbsp;Tobias Harm,&nbsp;Tatsiana Castor,&nbsp;Anne-Katrin Rohlfing,&nbsp;Meinrad Paul Gawaz","doi":"10.1016/j.bbrep.2025.102115","DOIUrl":"10.1016/j.bbrep.2025.102115","url":null,"abstract":"<div><div>Phosphodiesterase enzymes (PDEs) play a pivotal role in regulating platelet activity by modulating intracellular levels of cAMP and cGMP. Modulation of PDE-2, -3 and -5 activity by suitable inhibitors has been found to reduce platelet activity, and thus thrombus formation.</div><div>Our aim was to study Ibudilast effects on platelet activation, degranulation and aggregation. Therefore, we used the nonspecific PDE inhibitors IBMX as well as the PDE-5 inhibitor Sildenafil as controls. Platelet agonists collagen-related peptide (CRP-A), adenosine diphosphate (ADP) and thrombin receptor activator peptide (TRAP6) were used to induce distinct activation pathways. PDE inhibition was quantified by western blot analysis. Platelet activity was assessed using flow cytometry, light transmission aggregometry and in vitro thrombus formation.</div><div>Inhibition of all platelet PDEs by IBMX substantially reduced platelet activation and aggregation in response to all tested platelet agonists. Ibudilast preferentially inhibits PDE-3 in platelets. Ibudilast decreased platelet activation and aggregation induced by ADP and TRAP, but not CRP-A. Sildenafil alone induced no reduction in PDE activity, platelet activation or aggregation. However, the combination of Sildenafil and Ibudilast had an additive effect on platelet activation. Interestingly, all tested PDE inhibitors demonstrated a significant effect on platelet-dependent thrombus formation.</div><div>In conclusion, the effect of PDE inhibitors on platelet function is influenced by two primary factors: the pharmacological target of the inhibitor and the cAMP/cGMP interaction with the activation pathways induced. Platelet activation by ADP via P₂Y₁₂ and TRAP via PAR1 showed a greater response to PDE inhibitors than platelet activation by CRP via GPVI.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"43 ","pages":"Article 102115"},"PeriodicalIF":2.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}