Biology Direct最新文献

{"title":"Exploring the association between osteoporosis and kidney stones: a clinical to mechanistic translational study based on big data and bioinformatics.","authors":"Di Luo, Linguo Xie, Jingdong Zhang, Chunyu Liu","doi":"10.1186/s13062-025-00627-w","DOIUrl":"10.1186/s13062-025-00627-w","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis and kidney stones share several common pathophysiological risk factors, and their association is well-established. However, previous studies have primarily focused on environmental mediators, such as diet, and the precise mechanism linking these two conditions remains unclear.</p><p><strong>Methods: </strong>The relationship between osteoporosis and kidney stones was analyzed using weighted multivariate logistic regression, employing data from five cycles of the National Health and Nutrition Examination Survey (NHANES) from 2007-2010, 2013-2014, and 2017-2020. Gene expression data from the Gene Expression Omnibus (GEO) microarray database were integrated with machine learning techniques to identify key genes involved in both osteoporosis and kidney stones. Common targets were then identified through the Comparative Toxicogenomics Database (CTD) and GeneCards. GMFA enrichment analysis was performed to identify shared biological pathways. Additionally, drug prediction and molecular docking were employed to further investigate the pharmacological relevance of these targets.</p><p><strong>Results: </strong>Analysis of the NHANES database confirmed a strong association between osteoporosis and kidney stones. Weighted multivariate logistic regression showed that osteoporosis (OR: 1.41; 95% CI 1.11-1.79; P < 0.001) and bone loss (OR: 1.24; 95% CI 1.08-1.43; P < 0.001) were significantly correlated with an increased risk of kidney stones. Three hub genes-WNT1, AKT1, and TNF-were identified through various analytical methods. GMFA revealed that the mTOR signaling pathway is a key shared pathway. Molecular docking studies further confirmed the pharmacological relevance of these targets, demonstrating strong binding affinity between drugs and the proteins involved, consistent with previous findings.</p><p><strong>Conclusion: </strong>Bone loss is associated with an increased risk of kidney stones. Targeting the mTOR signaling pathway may offer a potential therapeutic approach for treating both osteoporosis and kidney stones.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"42"},"PeriodicalIF":5.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751127","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}

{"title":"The CXCR3/PLC/IP3-IP3R axis is responsible for the ignition of UPR in intestinal epithelial cells exposed to gliadin peptide, during the onset of celiac disease.","authors":"Romina Monzani, Mara Gagliardi, Valentina Saverio, Nausicaa Clemente, Alice Monzani, Ivana Rabbone, Francesca Nigrelli, Samuele Pellizzaro, Emanuele Ferrario, Silvia Saettone, Nico Pagano, Luigina De Leo, Dmitry Lim, Daniele Sblattero, Marco Corazzari","doi":"10.1186/s13062-025-00633-y","DOIUrl":"10.1186/s13062-025-00633-y","url":null,"abstract":"<p><strong>Background: </strong>Coeliac disease is an autoimmune disease that is primarily associated with chronic inflammation of the gut, but can also affect organs outside the gut, from the liver to the skin and CNS. The disease is triggered in predisposed individuals by a peptide mixture (PT) derived from the digestion of gliadin, a component of wheat, which is ingested with food. Although the induction of endoplasmic reticulum stress in intestinal epithelial cells (IECs) upon exposure to PT is known, the underlying molecular mechanisms remain unclear. Identifying the key players in this signaling pathway could therefore help to develop a new effective therapeutic strategy for the treatment of CD patients.</p><p><strong>Methods: </strong>Two CD models were used to identify the molecular mechanism linking extracellular PT and endoplasmic reticulum (ER) stress in the IECs of predisposed individuals exposed to gliadin. These models were an in vitro model based on CaCo-2 cells and an ex vivo model based on our previously described gut ex vivo system (GEVS), both exposed to PT.</p><p><strong>Results: </strong>Our results clearly show that the interaction of gliadin peptides with the transmembrane CXCR3 receptor on IECs leads to a rapid induction of PLC activity that generates IP3 molecules. This second messenger binds to the IP3R located in ER membranes, resulting in calcium efflux from the organelle.</p><p><strong>Conclusion: </strong>The PT-dependent ER stress observed in the IECs of CD patients results from the excessive release of calcium from the ER. Importantly, inhibition of this signaling pathway abrogates ER stress, which in turn attenuates downstream signs of CD, such as TG2 expression and gut permeability dysregulation, as well as inhibits inflammation.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"39"},"PeriodicalIF":5.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751037","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}

{"title":"Identification of druggable targets in acute kidney injury by proteome- and transcriptome-wide Mendelian randomization and bioinformatics analysis.","authors":"Jiachen Liu, Dianjie Zeng, Yinhuai Wang, Fei Deng, Shuiqing Wu, Zebin Deng","doi":"10.1186/s13062-025-00631-0","DOIUrl":"10.1186/s13062-025-00631-0","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) remains a critical condition with limited therapeutic options, predominantly managed by renal replacement therapy. The challenge of developing targeted treatments persists.</p><p><strong>Methods: </strong>We integrated genetic data related to druggable proteins and gene expression with AKI genome-wide association study (GWAS) findings. Based on multi-omics Mendelian randomization (MR), we identified the potential causal influence of 5,883 unique proteins and genes on AKI. We also performed using reverse MR and external cohort-based analysis to verify the robustness of this causal relationship. Expression patterns of these targets were examined using bulk transcriptome and single-cell transcriptome data. In addition, drug repurposing analyses were conducted to explore the potential of existing medications. We also constructed a molecular interaction network to explore the interplay between identified targets and known drugs.</p><p><strong>Results: </strong>Genetically predicted levels of seven proteins and twelve genes were associated with an increased risk of AKI. Of these, six targets (NCF1, TNFRSF1B, APEH, ACADSB, ADD1, and FAM3B) were prioritized based on robust evidence and validated in independent cohorts. Reverse MR showed a one-way causal relationship of targets. These targets are predominantly expressed in proximal tubular cells, endothelial cells, collecting duct-principal cells, and immune cells within both AKI-affected and normal tissues. Several promising drug repurposing opportunities were identified, such as telmisartan-NCF1, calcitriol-ACADSB, and ethinyl estradiol-ACADSB. The molecular interaction mapping and pathway integration analysis provided further insights, suggesting potential strategies for combinatorial therapies.</p><p><strong>Conclusions: </strong>This extensive investigation identified several promising therapeutic targets for AKI and highlighted opportunities for drug repurposing. These findings offer valuable insights that could shape future research and the development of targeted treatments.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"38"},"PeriodicalIF":5.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728599","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}

{"title":"c-Jun promotes neuroblastoma cell differentiation by inhibiting APC formation via CDC16 and reduces neuroblastoma malignancy.","authors":"Yunyun Wang, Jingjing Huang, Zhenhua Song, Shuo Zhang, Haojie Guo, Qi Leng, Na Fang, Shaoping Ji, Jian Yang","doi":"10.1186/s13062-025-00630-1","DOIUrl":"10.1186/s13062-025-00630-1","url":null,"abstract":"<p><p>Neuroblastoma is a pediatric embryonal malignancy characterized by impaired neuronal differentiation. Differentiation status in neuroblastoma strongly affects the clinical outcome, thus, enforcement of differentiation becomes a treatment strategy for this disease. However, the molecular mechanisms that control neuroblastoma differentiation are poorly understood. As an extensively studied protein of the activator protein-1 (AP-1) complex, c-Jun is involved in numerous cell regulations such as proliferation, survival and differentiation. In the current study, we demonstrated that c-Jun expression was upregulated by retinoic acid (RA) and flow cytometry assay indicated c-Jun overexpression arrested cell cycle to G1 phase, which, in turn, promoted the initiation of neuroblastoma cell differentiation. Co-immunoprecipitation (co-IP) assay showed that c-Jun competitively interacted with CDC16, a key subunit in anaphase-promoting complex (APC), resulting in reduced APC formation and inhibition of cell cycle progression. Furthermore, EdU proliferation assay and transwell experiment showed that c-Jun overexpression inhibited neuroblastoma cell proliferation and migration via interacting and sequestering CDC16. These findings identify c-Jun as a key regulator of neuroblastoma cell cycle and differentiation and may represent a promising therapeutic target to induce neuroblastoma differentiation via the interaction between c-Jun and CDC16.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"37"},"PeriodicalIF":5.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728598","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}

{"title":"Circulating extracellular vesicles regulate ELAVL1 by delivering miR-133a-3p which affecting NLRP3 mRNA stability inhibiting PANoptosome formation.","authors":"Deliang Wang, Zheng Dai, Lu Jiang, Ke Liu","doi":"10.1186/s13062-025-00605-2","DOIUrl":"10.1186/s13062-025-00605-2","url":null,"abstract":"<p><strong>Background: </strong>In the quest to elucidate novel therapeutic strategies for myocardial injury, recent investigations have underscored the pivotal roles played by circulating extracellular vesicles (EVs) in intercellular communication.</p><p><strong>Method: </strong>EVs were extracted from individuals who had experienced AMI-EVs and those who were N-EVs. To assess the impact of circulating EVs on cardiomyocyte and endothelial cell proliferation, apoptosis, migration, and tube formation, a range of in vitro assays such as CCK8, EdU assays, flow cytometry, wound healing assays and angiogenesis assays were conducted. Differentially expressed miRNAs in EVs were validated using microarray analysis and real-time PCR. Through bioinformatics analysis, ELAVL1 was identified as a potential downstream target of miR-133a-3p. This finding was further confirmed by conducting dual-luciferase reporter assay and RNA co-immunoprecipitation experiments. To investigate the regulatory effects of circulating EVs from various sources on myocardial injury and PANoptosis, an animal model of ischemia-reperfusion-induced myocardial injury was established.</p><p><strong>Result: </strong>Our findings revealed that circulating EVs effectively deliver miR-133a-3p to target cells, where it binds to ELAVL1, leading to a decrease in NLRP3 mRNA stability. This reduction in NLRP3 mRNA stability subsequently inhibits the assembly of the PANoptosome, a multi-protein complex implicated in PANoptosis. As a result, we observed a significant mitigation of PANoptosis in our myocardial injury models, demonstrating the protective role of miR-133a-3p against excessive cell death.</p><p><strong>Conclusion: </strong>The present study underscores the regulatory role of circulating EV-delivered miR-133a-3p in modulating PANoptosis through ELAVL1-mediated NLRP3 mRNA stabilization. This mechanism represents a potential therapeutic target for attenuating myocardial injury by suppressing PANoptosis.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"36"},"PeriodicalIF":5.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717799","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}

{"title":"Prognostic and immunological implications of protein kinases in gastric cancer: a focus on hub gene ABL2 and its impact on the polarization of M2 macrophages.","authors":"Di Chen, Ju Huang, Aiming Yang, Zhifan Xiong","doi":"10.1186/s13062-025-00636-9","DOIUrl":"10.1186/s13062-025-00636-9","url":null,"abstract":"<p><strong>Background: </strong>Protein kinases are essential cellular signal modulators involved in tumorigenesis, metastasis, immune response, and drug resistance. However, the comprehensive features and clinical significance of protein kinases in gastric cancer (GC) remain inconclusive.</p><p><strong>Methods: </strong>We analyzed the transcriptional profiles of protein kinases in GC patients from the GEO and TCGA databases. Based on differentially expressed kinase genes (DE-KGs), a novel cluster was identified to assess its association with patient survival and the tumor microenvironment (TME) in GC. Subsequently, an optimal DE-KGs-based model (DE-KGsM) was determined using 101 machine-learning algorithm combinations. This model was evaluated using multi-omics data to investigate its associations with patient prognosis, clinical features, tumor microenvironment, tumor-infiltrating immune cells (TIICs), and immunotherapy response. Furthermore, scRNA-seq analysis and TIMER algorithm were applied to determine the correlation between the hub gene (ABL2) in the DE-KGsM and Macrophages. Finally, in vitro experiments were performed to explore the immune-related mechanisms of ABL2 in GC.</p><p><strong>Results: </strong>We identified two molecular subtypes of GC patients based on 64 DE-KGs expression. Significant differences were observed in overall survival and TIIC characteristics between Cluster 1 and Cluster 2. Among these 64 DE-KGs, we identified an optimal DE-KGsM that could be a prognostic indicator in GC. TIICs and TIDE analyses exhibited that GC patients in the high-DE-KGsM score group had a higher proportion of M2 macrophages and lower response rates to ICI treatment. scRNA-seq analysis indicated that ABL2 might play an indispensable role in tumor immunity. Furthermore, in vitro experiments demonstrated that ABL2 accelerated the proliferation, migration, and invasion of GC cells, as well as the polarization of M2 macrophages.</p><p><strong>Conclusions: </strong>The DE-KGsM could be a powerful predictor of GC patients' survival and might facilitate the development of personalized therapy. Furthermore, as a hub gene in the DE-KGsM, ABL2 could be an immunological biomarker that modulates the polarization of M2 macrophages, thereby promoting GC progression.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"35"},"PeriodicalIF":5.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699685","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}

{"title":"Single-cell RNA sequencing reveals a new mechanism of endothelial cell heterogeneity and healing in diabetic foot ulcers.","authors":"Songyun Zhao, Hua Yu, Zihao Li, Wanying Chen, Kaibo Liu, Hao Dai, Gaoyi Wang, Zibing Zhang, Jiaheng Xie, Yucang He, Liqun Li","doi":"10.1186/s13062-025-00628-9","DOIUrl":"10.1186/s13062-025-00628-9","url":null,"abstract":"<p><p>Diabetic foot ulcers (DFU) are a common and severe complication among diabetic patients, posing a significant burden on patients' quality of life and healthcare systems due to their high incidence, amputation rates, and mortality. This study utilized single-cell RNA sequencing technology to deeply analyze the cellular heterogeneity of the skin on the feet ofDFU patients and the transcriptomic characteristics of endothelial cells, aiming to identify key cell populations and genes associated with the healing and progression of DFU. The study found that endothelial cells from DFU patients exhibited significant transcriptomic differences under various conditions, particularly in signaling pathways related to inflammatory responses and angiogenesis. Through trajectory analysis and cell communication research, we revealed the key role of endothelial cell subsets in the development of DFU and identified multiple important gene modules associated with the progression of DFU. Notably, the promoting effect of the SH3BGRL3 gene on endothelial cell proliferation, migration, and angiogenic capabilities under high glucose conditions was experimentally verified, providing a new potential target and theoretical basis for the treatment of DFU. This study not only enhances the understanding of the pathogenesis ofDFU but also provides a scientific basis for the development ofnew therapeutic strategies.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"34"},"PeriodicalIF":5.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690528","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}

{"title":"Doxorubicin PK/PD modeling in multiple myeloma: towards in silico trials.","authors":"Daniele Andrean, Francesco Da Ros, Mario Mazzucato, Morten Gram Pedersen, Roberto Visentin","doi":"10.1186/s13062-025-00626-x","DOIUrl":"10.1186/s13062-025-00626-x","url":null,"abstract":"<p><p>Doxorubicin (DOXO) is a well-known chemotherapy drug, which is widely used in the treatment of Multiple Myeloma (MM), a treatable but not curable type of blood cancer. Here, we propose a pharmacokinetics and pharmacodynamics (PK/PD) simulation environment, aimed at facilitating the optimization of DOXO treatment regimens in MM treatment. The resulting model has a transparent mechanistic structure, which facilitates its use and interpretation. The simulator was developed using a combination of experimental and modeling techniques, starting from in vitro PK/PD experiments conducted on MM cells. In our previous work, we carefully developed a PK model for DOXO in MM cells by fitting experimental data. We now devise a PD model from in vitro data investigating the effect of different concentrations of DOXO on cell growth and death in MM cell populations. The PK model is extended to enable a clear mechanistic link between the PK and the PD models, hence providing a complete PK/PD simulator. We show how the mathematical model can be exploited to simulate different DOXO administration protocols with different dosages, repetitions and exposure times, thus, making it possible to explore the effect of a wide range of treatment protocols easily.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"33"},"PeriodicalIF":5.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676823","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}

{"title":"Dualistic role of ZEB1 and ZEB2 in tumor progression.","authors":"Sergey E Parfenyev, Alexandra A Daks, Oleg Y Shuvalov, Olga A Fedorova, Nikolay B Pestov, Tatyana V Korneenko, Nickolai A Barlev","doi":"10.1186/s13062-025-00604-3","DOIUrl":"10.1186/s13062-025-00604-3","url":null,"abstract":"<p><p>It is generally accepted that ZEB1 and ZEB2 act as master regulators of the epithelial-mesenchymal transition, which arguably is the key mechanism of metastasis. Accordingly, they are deemed as negative predictors of the survival of cancer patients by promoting the emergence of secondary foci of the disease. Paradoxically, in some types of cancer types the opposite effect is observed, i.e. ZEB1 and ZEB2 are associated with better prognosis for cancer patients. In this review, we discuss the hypothesis that the tumorigenic effects of ZEB1/ZEB2 can be different in various tissues depending on the initial status of these proteins in the corresponding healthy tissues. Emerging evidence suggests that ZEB1 and ZEB2 are constitutively expressed in several healthy tissues, performing vital functions. Consequently, reducing the expression of ZEB1 and ZEB2 could negatively affect these tissues causing various diseases, including cancer. Finally, the dualistic role of ZEB1 and ZEB2 as immune modulators and their effect on tumor microenvironment is also discussed.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"32"},"PeriodicalIF":5.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668929","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}

{"title":"Plasma N-Glycoproteomics in monozygotic twin pairs discordant for body mass index reveals an obesity signature related to inflammation and iron metabolism.","authors":"Maheswary Muniandy, Sakari Joenväärä, Birgitta W van der Kolk, Tiialotta Tohmola, Hanna Haltia, Sina Saari, Antti Hakkarainen, Jesper Lundbom, Juho Kuula, Per-Henrik Groop, Jaakko Kaprio, Sini Heinonen, Risto Renkonen, Kirsi H Pietiläinen","doi":"10.1186/s13062-025-00609-y","DOIUrl":"10.1186/s13062-025-00609-y","url":null,"abstract":"<p><strong>Background: </strong>N-glycosylation is a complex, post-translational modification which influences protein function and is sensitive to physiological changes. Obesity is associated with alterations in protein function; however, little is known about the glycoproteome in obesity beyond observations of association with types and structures of selected glycopeptides. Most often, due to technical challenges, glycan composition and structure information are missing. Here, we combined label-free data-independent proteomics and targeted quantitative glycoproteomics to study N-glycosylation of plasma proteins in obesity. Using a monozygotic twin study design, we controlled for genetic variation and focused only on the acquired effects of obesity.</p><p><strong>Methods: </strong>Using plasma samples of 48 monozygotic twin pairs discordant for BMI (intrapair difference > 2.5 kg/m²), we identified using mass spectrometry, differential protein and glycopeptide levels between heavier and leaner co-twins. We used a within-twin paired analysis model and considered p < 0.05 as significant.</p><p><strong>Results: </strong>We identified 48 protein and 33 N-glycosylation expression differences (p < 0.05) between co-twins. These differences occurred either both in the protein expression and glycoprotein (sometimes in opposing directions) or independently from each other. Haptoglobin protein was upregulated (Fold Change = 1.10, p = 0.001) in heavier co-twins along with seven upregulated glycan compositions at N-glycosylation site Asn241. The complement protein C3 was upregulated (Fold Change = 1.08, p = 0.014) along with one upregulated glycopeptide at Asn85. Additionally, many glycopeptides were upregulated despite non-significant differences in protein-backbone plasma levels.</p><p><strong>Conclusion: </strong>Differential protein expression related to cholesterol biosynthesis and acute phase signalling as well as N-glycosylation of proteins related to iron metabolism and inflammation can be linked to acquired obesity.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"20 1","pages":"31"},"PeriodicalIF":5.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662581","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}