Frontiers in Molecular Biosciences最新文献

{"title":"Glycosyltransferases: glycoengineers in human milk oligosaccharide synthesis and manufacturing.","authors":"Alanna S Slater, Andrew G McDonald, Rita M Hickey, Gavin P Davey","doi":"10.3389/fmolb.2025.1587602","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1587602","url":null,"abstract":"<p><p>Human milk oligosaccharides (HMOs) are a diverse group of complex carbohydrates that play crucial roles in infant health, promoting a beneficial gut microbiota, modulating immune responses, and protecting against pathogens. Central to the synthesis of HMOs are glycosyltransferases, a specialized class of enzymes that catalyse the transfer of sugar moieties to form the complex glycan structures characteristic of HMOs. This review provides an in-depth analysis of glycosyltransferases, beginning with their classification based on structural and functional characteristics. The catalytic activity of these enzymes is explored, highlighting the mechanisms by which they facilitate the precise addition of monosaccharides in HMO biosynthesis. Structural insights into glycosyltransferases are also discussed, shedding light on how their conformational features enable specific glycosidic bond formations. This review maps out the key biosynthetic pathways involved in HMO production, including the synthesis of lactose, and subsequent fucosylation and sialylation processes, all of which are intricately regulated by glycosyltransferases. Industrial methods for HMO synthesis, including chemical, enzymatic, and microbial approaches, are examined, emphasizing the role of glycosyltransferases in these processes. Finally, the review discusses future directions in glycosyltransferase research, particularly in enhancing the efficiency of HMO synthesis and developing advanced analytical techniques to better understand the structural complexity and biological functions of HMOs.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1587602"},"PeriodicalIF":3.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Cuscutae Semen</i> in depression-induced ovarian dysfunction: metabolomics with UPLC-QToF-MS in female mice.","authors":"Ying Xie, Zhaoxiang Zeng, Jinrong Zhang, Qiangqiang Han, Chengwu Song, Shuna Jin, Min Zhao","doi":"10.3389/fmolb.2025.1595602","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1595602","url":null,"abstract":"<p><p>The increasing prevalence of depression profoundly affects female ovarian health. Although <i>Cuscutae Semen</i> (CS) is acknowledged for treating reproductive disorders, its pharmacological mechanisms in depression-induced ovarian dysfunction remain insufficiently explored. This study investigated CS's effects in a chronic unpredictable mild stress (CUMS) mouse model of depression. Mice were divided into control, CUMS model, CS treatment and estradiol treatment group. Behavioral and biochemical analyses assessed depressive-like behaviors and hormone levels. Untargeted metabolomics utilizing ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied to identify differential metabolites of CS in the treatment of depression-induced ovarian dysfunction. These findings were confirmed through real-time quantitative polymerase chain reaction assays. Based on the outcomes from behavioral and biochemical assays, CS effectively ameliorated the chronic unpredictable mild stress-induced reproductive ailment in mice. Ten differential metabolites were identified, highlighting the impact of CUMS and CS's ameliorative effects. Pathways linked to arachidonic acid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and steroid hormone biosynthesis were involved. Seven target genes further validated the metabolomic analysis. This study provides strong evidence of CS's therapeutic potential in alleviating depression-induced ovarian dysfunction, shedding light on its pharmacological mechanisms and supporting its use as a functional medical food.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1595602"},"PeriodicalIF":3.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the role of histone acetylation in sepsis biomarker discovery.","authors":"Feng Cheng, Juxin Deng, Zhaoyang Du, Lei Li, Zhaolei Qiu, Min Zhu, Hongchang Zhao, Zhenjie Wang","doi":"10.3389/fmolb.2025.1582181","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1582181","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. Despite advances in clinical care, effective biomarkers for early diagnosis and prognosis remain lacking. Emerging evidence suggests that histone acetylation plays a crucial role in the pathophysiology of sepsis.</p><p><strong>Methods: </strong>Transcriptomic and single-cell RNA sequencing data were used to identify histone acetylation-related genes. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed, followed by machine learning algorithms (LASSO, SVM-RFE, and Boruta) to screen for potential biomarkers. Mendelian randomization (MR), RT-qPCR, and functional assays were conducted for validation.</p><p><strong>Results: </strong><i>BLOC1S1</i>, <i>NDUFA1</i>, and <i>SFT2D1</i> were identified as key biomarkers. A predictive nomogram demonstrated strong diagnostic potential. Immune infiltration and single-cell analyses linked the biomarkers to macrophage activity. MR analysis confirmed <i>SFT2D1</i> as a causal factor in sepsis. Functional assays showed that knockdown of <i>SFT2D1</i> suppressed <i>CXCL10</i> and <i>IL-6</i> expression, indicating its pro-inflammatory role.</p><p><strong>Discussion: </strong>This study identifies novel biomarkers associated with histone acetylation and immune dysregulation in sepsis. These findings deepen our understanding of sepsis pathogenesis and may facilitate the development of improved diagnostic and therapeutic strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1582181"},"PeriodicalIF":3.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type-2 diabetes epigenetic biomarkers: present status and future directions for global and Indigenous health.","authors":"Sarah Munns, Alex Brown, Sam Buckberry","doi":"10.3389/fmolb.2025.1502640","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1502640","url":null,"abstract":"<p><p>Type-2 diabetes is a systemic condition with rising global prevalence, disproportionately affecting Indigenous communities worldwide. Recent advances in epigenomics methods, particularly in DNA methylation detection, have enabled the discovery of associations between epigenetic changes and Type-2 diabetes. In this review, we summarise DNA methylation profiling methods, and discuss how these technologies can facilitate the discovery of epigenomic biomarkers for Type-2 diabetes. We critically evaluate previous DNA methylation biomarker studies, particularly those using microarray platforms, and advocate for a shift towards sequencing-based approaches to improve genome-wide coverage. Furthermore, we emphasise the need for biomarker studies that include genetically diverse populations, especially Indigenous communities who are significantly impacted by Type-2 diabetes. We discuss research approaches and ethical considerations that can better facilitate Type-2 diabetes biomarker development to ensure that future genomics-based precision medicine efforts deliver equitable health outcomes. We propose that by addressing these gaps, future research can better capture the genetic and environmental complexities of Type-2 diabetes among populations at disproportionate levels of risk, ultimately leading to more effective diagnostic and therapeutic strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1502640"},"PeriodicalIF":3.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-based deep learning with clinical and imaging features to differentiate medulloblastoma and ependymoma in children.","authors":"Yasen Yimit, Parhat Yasin, Yue Hao, Abudouresuli Tuersun, Chencui Huang, Xiaoguang Zou, Ya Qiu, Yunling Wang, Mayidili Nijiati","doi":"10.3389/fmolb.2025.1570860","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1570860","url":null,"abstract":"<p><strong>Background: </strong>Medulloblastoma (MB) and ependymoma (EM) in children share similarities in terms of age group, tumor location, and clinical presentation, which makes it challenging to clinically diagnose and distinguish them.</p><p><strong>Purpose: </strong>The present study aims to explore the effectiveness of T2-weighted magnetic resonance imaging (MRI)-based deep learning (DL) combined with clinical imaging features for differentiating MB from EM.</p><p><strong>Methods: </strong>Axial T2-weighted MRI sequences obtained from 201 patients across three study centers were used for model training and testing. The regions of interest were manually delineated by an experienced neuroradiologist with supervision by a senior radiologist. We developed a DL classifier using a pretrained AlexNet architecture that was fine-tuned on our dataset. To mitigate class imbalance, we implemented data augmentation and employed K-fold cross-validation to enhance model generalizability. For patient classification, we used two voting strategies: hard voting strategy in which the majority prediction was selected from individual image slices; soft voting strategy in which the prediction scores were averaged across slices with a threshold of 0.5. Additionally, a multimodality fusion model was constructed by integrating the DL classifier with clinical and imaging features. The model performance was assessed using a 7:3 random split of the dataset for training and validation, respectively. The key metrics like sensitivity, specificity, positive predictive value, negative predictive value, F1 score, area under the receiver operating characteristic curve (AUC), and accuracy were calculated, and statistical comparisons were performed using the DeLong test. Thereafter, MB was classified as positive, while EM was classified as negative.</p><p><strong>Results: </strong>The DL model with the hard voting strategy achieved AUC values of 0.712 (95% confidence interval (CI): 0.625-0.797) on the training set and 0.689 (95% CI: 0.554-0.826) on the test set. In contrast, the multimodality fusion model demonstrated superior performance with AUC values of 0.987 (95% CI: 0.974-0.996) on the training set and 0.889 (95% CI: 0.803-0.949) on the test set. The DeLong test indicated a statistically significant improvement in AUC values for the fusion model compared to the DL model (<i>p</i> < 0.001), highlighting its enhanced discriminative ability.</p><p><strong>Conclusion: </strong>T2-weighted MRI-based DL combined with multimodal clinical and imaging features can be used to effectively differentiate MB from EM in children. Thus, the structure of the decision tree in the decision tree classifier is expected to greatly assist clinicians in daily practice.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1570860"},"PeriodicalIF":3.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response.","authors":"Haiqi Lu, Zelin Lu, Yufei Wang, Miaoqin Chen, Guangliang Li, Xian Wang","doi":"10.3389/fmolb.2025.1604313","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1604313","url":null,"abstract":"<p><p>The APOBEC (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like) family of cytidine deaminases has emerged as pivotal a contributor to genomic instability and adaptive immunity through DNA/RNA editing. Accumulating evidence underscores their dual role in breast carcinogenesis-driving tumor heterogeneity via mutagenesis while simultaneously shaping immunogenic landscapes. This review synthesizes current insights into APOBEC-mediated molecular mechanisms, focusing on their clinical implications across breast cancer subtypes. Notably, APOBEC-driven mutagenesis correlates with elevated tumor mutational burden (TMB), replication stress vulnerability, and immune checkpoint inhibitor (ICI) responsiveness. Paradoxically, these mutations also accelerate endocrine therapy resistance and subclonal diversification. We propose APOBEC mutational signatures as predictive biomarkers for ICI efficacy and discuss therapeutic strategies leveraging APOBEC activity, including ATR inhibition and hypermutagenic immunotherapy. Harnessing APOBEC's duality-balancing its pro-immunogenic effects against genomic chaos-may redefine precision oncology in breast cancer.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1604313"},"PeriodicalIF":3.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MS4A7 based metabolic gene signature as a prognostic predictor in lung adenocarcinoma.","authors":"Yan Jiang, Zhengyu Shu, Lei Cheng, Haowei Wang, Taiping He, Liwen Fu, Chao Zhao, Xuefei Li, Weicheng Zeng","doi":"10.3389/fmolb.2025.1591446","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1591446","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) represents the most common form of lung cancer, contributing to significant global mortality. Metabolic reprogramming in tumor cells has been increasingly recognized as a hallmark of tumorigenesis, contributing to an immunosuppressive microenvironment. Given the promising prediction value of metabolism-related genes in LUAD, this study aims to explore the role of MS4A7, a member of the MS4A gene family, in LUAD prognosis and immune microenvironment dynamics.</p><p><strong>Methods: </strong>A prognostic signature for LUAD was developed using the LASSO-Cox regression algorithm with RNA-seq data from 500 LUAD patients in The Cancer Genome Atlas database. Genes with differential expression linked to metabolic pathways were identified, and 20 genes were included to develop a risk signature. Further functional enrichment analysis was conducted to compare the biological pathways activated in high-risk versus low-risk groups. Single-cell RNA sequencing was employed to identify the expression profile and role of MS4A7 in different macrophage populations within the LUAD.</p><p><strong>Results: </strong>The constructed prognostic model displayed high predictive accuracy, outperforming single gene-based predictions. High-risk patients exhibited significantly poorer survival outcomes. Pathway enrichment analysis revealed dysregulated metabolic pathways in high-risk patients, including activation of glycolysis, mTORC1 signaling, and ROS production. Single-cell RNA sequencing revealed that MS4A7 expression was predominantly found in macrophage populations, with high expression localized in MS4A7+ macrophages. These macrophages exhibited distinct metabolic reprogramming and key immune functions, particularly in crosstalk with T cells and neutrophils.</p><p><strong>Conclusion: </strong>The MS4A7 gene plays a critical role in LUAD prognosis, particularly through its involvement in immune modulation within the TME. MS4A7⁺ macrophages, characterized by distinct metabolic reprogramming and immune interactions, are pivotal in shaping LUAD progression and immune response. The findings highlight the potential of MS4A7 as a novel prognostic biomarker and therapeutic target for LUAD. Further investigation into the metabolic and immune regulatory mechanisms of MS4A7⁺ macrophages could offer new insights into LUAD treatment strategies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1591446"},"PeriodicalIF":3.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Colpomenia sinuosa</i> extract mitigates lead acetate-induced testicular dysfunctions in male rats.","authors":"Layla A Almutairi, Amal S Abu-Almakarem, Noorah Saleh Al-Sowayan, Sahar Abdulrahman Alkhodair, Hayat M Albishi, Thamir M Eid, Fahad A Alshanbari, Najlaa Yousef Abuzinadah, Maysa A Mobasher, Karim Samy El-Said","doi":"10.3389/fmolb.2025.1551773","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1551773","url":null,"abstract":"<p><strong>Background: </strong><i>Colpomenia sinuosa</i> brown alga contains pharmacologically active compounds with a wide spectrum of bioactivities; however, few studies have been conducted in the Mediterranean to assess their effects against heavy metal toxicity. One common non-biodegradable contaminant that poses a serious risk to human health and the environment is lead (Pb). This study investigated the efficacy of <i>C. sinuosa</i> extract (CSE) treatment on testicular injury caused by lead acetate (PbAc) in rats.</p><p><strong>Methods: </strong>The phytochemical, GC/MS profiling, and metal chelation ability of CSE were evaluated. Molecular docking studies were performed using AutoDock Vina. The oral LD₅₀ of CSE was determined by probit analysis. 40 male rats were used as follows: Gp1 as a negative control; Gp2 was treated with 1/10 of CSE LD₅₀ (340 mg/kg b. wt.); Gp3 was administered PbAc solution (100 mg/kg b. wt.); Gp4 was orally administered PbAc as in Gp3 and CSE as in Gp2. All treatments were given daily by gastric tube for 30 days. Body weight changes, biochemical, molecular, and histopathological examinations were investigated.</p><p><strong>Results: </strong>The results demonstrate that CSE exerted a pronounced metal-chelating activity <i>in vitro</i> and contain promising phytochemicals. The LD₅₀ of CSE was 3,400 mg/kg b. wt. PbAc-treated rats reported significant testicular dysfunction with impaired semen analysis, biochemical, molecular, and histological changes. CSE treatment showed significant palliative effects on these dysfunctions via improvements in antioxidant status, anti-inflammatory properties, and histopathological alterations. Interestingly, CSE treatment modulates the JAK2/STAT3, and NLRP3/Caspase-1 pathways axis in PbAc-injured rats.</p><p><strong>Conclusion: </strong>This study for the first time investigated the biochemical and molecular mechanisms regarding the effects of CSE treatment on PbAc-induced testicular damage in male rats. CSE showed potential attenuative effect on the testis injury induced by PbAc treatment by targeting JAK2/STAT3, and NLRP3/Caspase-1 pathways. These findings suggest that CSE could be used against the adverse effect of PbAc on male repro-toxicity.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1551773"},"PeriodicalIF":3.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors of colorectal cancer in middle-aged and elder adults in China: findings from the China health and retirement longitudinal study.","authors":"Lin Zhang, Yuyan Zhang, Yujia Huo, Yang Zhao, Aimin Xu, Zhining Liu, Qiaojun Hong, Huiming Tu, Junjie Huang, Li Liu","doi":"10.3389/fmolb.2025.1333834","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1333834","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to identify risk factors of colorectal cancer in a middle-aged and elder Chinese population over 45 years old and to provide evidence for preventing colorectal cancer in China.</p><p><strong>Method: </strong>The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative cohort used for research on demography, lifestyle and characteristics of colorectal cancer population. The logistic regression model was used to estimate the odds ratio (OR) and corresponding confidence interval (95% CI) using the maximum likelihood method. Univariate logistic regression was performed with the ORs of each risk factor and its association with incidence of colorectal cancer. Risk factors significant in univariate logistic regression were further evaluated by multivariate logistic regression. Cox proportional hazards model estimated the hazard ratio (HR) of each risk factor and its association with incidence of colorectal cancer.</p><p><strong>Results: </strong>In the univariable analysis, sex (OR = 2.31, 95% CI: 1.00-5.36, p = 0.05), smoking (OR = 2.30, 95% CI: 1.03-5.13, p = 0.04), age of quit drinking (OR = 1.07, 95% CI: 1.01-1.14, p = 0.02) and chronic lung disease (OR = 2.79, 95% CI: 1.11-6.99, p = 0.03) were associated with colorectal cancer which was also included in the multivariable analysis. However, probably because of the small sample size of colorectal cancer patients, no indicator was confirmed to be risk factor of colorectal cancer in the multivariable logistic regression. The univariate analysis of the Cox model indicated that smoking (HR = 2.30, 95%: 1.03-5.13, p = 0.04) and chronic lung disease (HR = 2.79, 95%: 1.11-6.97, p = 0.03) were associated with incidence of colorectal cancer. Similar to the results of multiple linear regression, no indicator was confirmed to be risk factors of incidence of colorectal cancer in the multivariable Cox model.</p><p><strong>Conclusion: </strong>In the univariate analysis, we identified significant associations between colorectal cancer and factors such as smoking and chronic lung disease. However, these associations did not hold in the multivariate analysis due to limitations in sample size. This suggests the need for further validation of these potential risk factors in larger-scale studies.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1333834"},"PeriodicalIF":3.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization.","authors":"Jilei Li, Jiarui Cao, Zhenyu Zhang, Sizhe Wang, Meng Zhu, Lili Yang, Wenhui Ouyang, Chunzheng Ma","doi":"10.3389/fmolb.2025.1580874","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1580874","url":null,"abstract":"<p><strong>Objective: </strong>To address the core pathological features of intestinal barrier disruption and immune imbalance in ulcerative colitis (UC), we developed a nano-targeted formulation (GGQL nano-preparation) based on berberine, puerarin, baicalin, and glycyrrhizin by combining traditional Chinese medicine (TCM) and nanotechnology in this study. We aimed to investigate whether GGQL nano-preparation could promote M2 macrophage polarization, correct intestinal inflammation, and treat UC.</p><p><strong>Methods: </strong>We used databases to identify M2 macrophage-related gene targets for GGQL nano-preparation in UC. Protein-protein interaction networks, topological analysis, and GO/KEGG enrichment analyses revealed GGQL nano-preparation's potential regulation of macrophage polarization via a specific pathway. We validated this using a dextran sulfate sodium (DSS)-induced UC model in C57BL/6 mice. Parameters assessed included the disease activity index (DAI), colon length, colitis macroscopic damage index (CMDI), spleen index, and pathological changes (via HE staining). Immunohistochemistry detected AMPK-PPAR axis factor changes to determine GGQL nano-preparation's impact on M2 macrophage polarization and intestinal inflammation.</p><p><strong>Results: </strong>Our analyses suggested the GGQL nano-preparation reduced the DAI, enhanced colon length, improved CMDI scores, and mitigated splenic inflammation. HE staining showed GGQL nano-preparation alleviated inflammation in the spleen, lungs, and colon. Immunohistochemical findings indicated GGQL nano-preparation upregulated AMPK, PPAR, and SIRT1 expression. Mechanistically, GGQL nano-preparation promoted M2 macrophage polarization through the AMPK-PPARγ axis, achieving therapeutic objectives for UC.</p><p><strong>Conclusion: </strong>The GGQL nano-preparation effectively promotes M2 macrophage polarization via the AMPK-PPARγ axis, treating UC.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1580874"},"PeriodicalIF":3.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}