Molecular and Cellular Biochemistry最新文献

{"title":"Glycosylation in cancer: mechanisms, diagnostic markers, and therapeutic applications.","authors":"Zahraa Qusairy, Miran Rada","doi":"10.1007/s11010-025-05303-1","DOIUrl":"10.1007/s11010-025-05303-1","url":null,"abstract":"<p><p>Glycosylation, a key post-translational modification, plays a pivotal role in cancer progression by influencing critical processes such as protein folding, immune modulation, and intercellular signaling. Altered glycosylation patterns are increasingly recognized as fundamental drivers of tumorigenesis, contributing to key cancer hallmarks like enhanced tumor migration, metastasis, and immune evasion. These aberrant glycosylation signatures not only offer insights into cancer biology but also serve as valuable diagnostic markers and potential therapeutic targets across a range of malignancies. This review explores the mechanisms underlying glycosylation alterations in cancer. We discuss the molecular basis of these changes, including genetic mutations, epigenetic regulation, and oncogene-driven shifts in glycosylation pathways. Additionally, we highlight recent advancements in glycomics research, with a focus on how these alterations influence tumor progression, angiogenesis, and the tumor microenvironment. Furthermore, the review considers the clinical implications of glycosylation changes, including their role in resistance to anti-cancer therapies and their potential as biomarkers for personalized treatment strategies. By bridging fundamental glycosylation research with clinical applications, this review underscores the promise of glycosylation as both a diagnostic tool and a therapeutic target in oncology, offering new avenues for improved patient stratification and precision medicine.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4941-4959"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic potential of annexin A1-derived peptide Ac_2-26 in modulating NLRP3 inflammasome activation in Crohn's disease.","authors":"Izabella Lice, Henrique T K Ito, Rebeca D Correia-Silva, Diego D Santos, Gisela R S Sasso, Paulo C Franco, Ricardo Artigiani, Karin V Greco, Cristiane D Gil","doi":"10.1007/s11010-025-05311-1","DOIUrl":"10.1007/s11010-025-05311-1","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) remains a complex and multifaceted condition, with its management dependent on a thorough understanding of its underlying mechanisms. While the ANXA1-FPR axis is implicated in the pathogenesis of IBD, its relationship with the NLRP3 inflammasome in this context has not been established. Thus, this study aimed to elucidate the intricate relationship between ANXA1, FPRs, and the NLRP3 inflammasome in the pathogenesis of IBD. For this purpose, mRNA and protein expression of ANXA1, FPRs, and NLRP3 inflammasome were analyzed using transcriptomic data (GSE179285) and immunohistochemistry on ileum and colon samples from CD patients and healthy controls. In vitro, ANXA1-derived peptide Ac_2-26's effect was tested on TNF-α-activated Caco-2 cells. Transcriptome analysis of GSE179285 revealed significantly increased levels of ANXA1, FPR1, FPR2, and NLRP3 transcripts in inflamed CD segments compared to controls. Immunohistochemistry confirmed these findings, showing strong immunoreactivity for ANXA1, FPR2, and NLRP3 in CD samples, particularly in the intestinal epithelium and inflammatory infiltrate. In vitro, ANXA1 and NLRP3 were co-expressed in Caco-2 cells stimulated with TNF-α. The peptide Ac_2-26 at 2 ng/mL significantly increased caspase-1 and IL-1β levels, enhancing NLRP3 inflammasome activation. Ac_2-26 also reduced ROS production and preserved epithelial integrity by enhancing occludin and cadherin expression. Overall, this study highlights the crucial role of ANXA1-FPR axis in regulating inflammation in CD and its potential therapeutic implications. Ac_2-26 modulates NLRP3 inflammasome activation and oxidative stress, preserves epithelial barrier integrity, and shows promise as a therapeutic target for IBD treatment.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5141-5155"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The alleviating effect of Bai-Ju essence on atopic dermatitis through anti-inflammatory and skin barrier repair mechanisms.","authors":"Congcong Zhu, Junchao Wu, Ya Chen, Tianyou Ma, Huijun Pan, Chuntao Zhai, Zongguang Tai, Zhongjian Chen, Quangang Zhu","doi":"10.1007/s11010-025-05270-7","DOIUrl":"10.1007/s11010-025-05270-7","url":null,"abstract":"<p><p>Bai-Ju essence (BJE) is a bioactive formulation composed of medicinal plant extracts, utilized in skincare products for its therapeutic potential. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation. This study aimed to evaluate BJE anti-inflammatory and skin-protective effects, and its potential mechanisms in treating AD. The ability of BJE to restore the epidermal barrier was assessed in HaCaT cells. In LPS-induced RAW264.7 cells, the anti-inflammatory potential of BJE was evaluated by measuring NO, IL-6, PGE2, and TNF-α. Western blot analysis was used to assess the regulation of the MAPK pathway. An in vivo AD-like mouse model was established using MC903, and measurements of body weight, ear thickness, and AD symptoms were recorded. Histological analysis quantified mast cell infiltration, while western blot determined FLG, LOR, and ELOVL6 expression. ELISA was used to measure TNF-α, IgE, IL-4, and IL-13 levels. Flow cytometry assessed the effect of BJE on Th cell phenotypes. BJE significantly enhanced skin barrier protein expression (CERS2, LOR, HAS-1, HAS-2, FLG) in HaCaT cells. It significantly reduced the levels of NO, IL-6, PGE2, and TNF-α in LPS-treated RAW264.7, demonstrating its anti-inflammatory potential. Mechanistically, BJE inhibited MAPK activation. BJE decreased ear thickness, improved skin lesions, and relieved AD symptoms in AD-like mice. In addition, BJE effectively suppressed mast cell infiltration and hyperkeratosis. BJE also decreased levels of TNF-α, IgE, IL-4, and IL-13 while increasing LOR, ELOVL6, and FLG expressions. Furthermore, BJE modulated Th1, Th2, and Th17 cell proportions. BJE promoted epidermal barrier repair in HaCaT, suppressed the LPS-induced inflammation in RAW264.7, enhanced the skin barrier integrity in AD-like mice, and exhibited immunomodulatory effects by restoring Th cell balance. These findings highlighted the therapeutic potential of BJE in AD through its dual action of anti-inflammation and skin barrier restoration.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5059-5074"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD44 and SLC1A2 are commonly regulated but do not form a fusion transcript in ER+ breast cancer.","authors":"Francesca Bonechi, Marina Bacci, Nicla Lorito, Alfredo Smiriglia, Edoardo Pagliantini, Matteo Benelli, Icro Meattini, Andrea Morandi","doi":"10.1007/s11010-025-05308-w","DOIUrl":"10.1007/s11010-025-05308-w","url":null,"abstract":"<p><p>Endocrine therapy (ET) is essential for managing ER+ HER2- breast cancer; however, resistance remains a significant clinical challenge. This study investigated whether CD44-SLC1A2 gene fusions, reported in gastrointestinal malignancies, contribute to ET resistance mechanisms in breast cancer. Although no CD44-SLC1A2 fusions were detected, high expression of CD44 and SLC1A2 was associated with poor survival outcomes and identified a therapy-resistant subpopulation sustained by aspartate and glutamate metabolism, highlighting potential metabolic vulnerabilities for future therapeutic intervention.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5173-5179"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132637","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 transcription revealing key transcription factors in embryonic kidney development.","authors":"Jingxian Huang, Bing Yan, Hongwei Wu, Hougang Yang, Shaodong Luan, Haiyan Yu, Wei Shi, Pingping Ye, Fang Yuan, Qiang Yan, Fanna Liu, Lianghong Yin, Donge Tang, Yong Dai","doi":"10.1007/s11010-025-05307-x","DOIUrl":"10.1007/s11010-025-05307-x","url":null,"abstract":"<p><p>The development of the kidney is a complex process involving the differentiation of renal progenitor cells into various specialized cell types, including renal tubular epithelial cells and podocytes. Understanding the molecular mechanisms that govern this differentiation process is crucial for unraveling the intricacies of kidney development. Recent advances in single-cell RNA sequencing technology have enabled researchers to explore the heterogeneity of renal progenitor cells at an unprecedented resolution, offering new insights into the distinct subpopulations and transcriptional landscapes within these cells. Our analysis revealed the presence of distinct subpopulations within renal progenitor cells. Furthermore, we identified key transcription factors that are crucial for the differentiation of these progenitors into renal tubular epithelial cells and podocytes. These findings provide new insights into the molecular mechanisms of kidney development, highlighting the role of specific transcription factors in the differentiation of renal progenitor cells. Although further research is needed to fully validate these findings and their therapeutic potential, this study provides a valuable foundation for future exploration of kidney regeneration strategies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5075-5089"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111409","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":"Dysregulated homocysteine metabolism and cardiovascular disease and clinical treatments.","authors":"Xiangyu Cao, Tingyu Wang, Gaohang Mu, Yupeng Chen, Bo Xiang, Jingze Zhu, Zhenya Shen","doi":"10.1007/s11010-025-05284-1","DOIUrl":"10.1007/s11010-025-05284-1","url":null,"abstract":"<p><p>Elevated homocysteine (Hcy) levels, known as hyperhomocysteinemia (HHcy), are recognized as a separate risk factor for cardiovascular disease. Mutations in methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta synthase (CBS)-enzymes pivotal at the juncture of the trans-sulfuration and remethylation pathways-underlie the pathogenesis of HHcy. Although vitamin supplementation has been proven to effectively decrease Hcy levels, there is still uncertainty about whether this reduction translates to a decrease in the incidence rates from cardiovascular diseases (CVDs). This review seeks to explore the linking between Hcy and specific diseases, the role of Hcy in vascular homeostasis, and the research on the possible advantages of therapies designed to lower Hcy levels. Understanding the intricate mechanisms of their metabolism and interactions is essential for pharmacological treatments to mitigate the adverse effects associated with metabolic dysregulation of Hcy. Given the widespread availability and ease of use of Hcy test kits, we strongly advocate for the routine administration of rapid blood tests for individuals at high risk of CVDs, particularly among the elderly population.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4907-4920"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017716","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":"Radial artery intima-media thickening is a sensitive marker of atherosclerosis and coronary artery stenosis, a lesson from a 6-year study of a spontaneous monkey model.","authors":"Jue Wang, Wen Zheng, Haibao Shang, Lin Pan, Ye Yuan, Wenli Chen, Chunguang Guo, Shihan Li, Xueting Sun, Jing Guo, Xiuqin Zhang","doi":"10.1007/s11010-025-05315-x","DOIUrl":"10.1007/s11010-025-05315-x","url":null,"abstract":"<p><p>Atherosclerosis is the primary driver of cardiovascular and cerebral vascular diseases globally. Atherosclerotic plaques have been detected in multiple arterial locations, such as the aorta, carotids, and coronaries. However, it remains uncertain if there are variations in susceptibility and association among arteries of different calibers. Utilizing a spontaneous rhesus monkey model of metabolic syndrome (MetS), we assessed the susceptibility of atherosclerosis among the radial artery, femoral artery, and carotid artery and their correlation with coronary heart disease (CHD). The development of atherosclerosis in the three arteries mentioned above was evaluated by Intima-media thickness (IMT) and plaques using echo imaging over 6 years in a cohort of elderly monkeys with metabolic disorders. Coronary artery stenosis was assessed by coronary flow reserve (CFR) simultaneously. The diagnosis was further confirmed by histopathological examination, and RNA sequencing was employed to probe the transcriptional underpinnings of atherosclerotic development. The spontaneous development of atherosclerosis was observed in elderly monkeys, and the incidence of atherosclerosis was increased by three times in the MetS monkeys compared to the age-matched control group. During the 6-year follow-up, there was a notable increase in the IMT across all three arteries, with the radial artery showing the most pronounced thickening. Moreover, only the radial IMT correlated with CFR, suggesting its potential as a non-invasive diagnostic indicator for CHD. Histopathology confirmed the findings by echo imaging and identified different extracellular matrix (ECM) remodeling patterns in the arteries. In addition, transcriptomic analysis revealed that ECM remodeling and inflammation-related pathways were significantly upregulated in radial atherosclerotic samples, multiple inflammatory pathways were upregulated in the femoral lesion samples, and the carotid samples failed to enrich any pathways due to a lack of differentially expressed genes compared to the control samples. Non-human primates, which share extensive genetic and physiological similarities with humans, develop atherosclerosis spontaneously. This provides an invaluable platform for investigating the intricate mechanisms of arterial disease and evaluating potential treatments. Using the monkey model, we identified the radial artery as a sensitive indicator for assessing the occurrence and progression of atherosclerosis and coronary stenosis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5181-5195"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136112","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":"Targeting mitochondrial dysfunction: an innovative strategy for treating renal fibrosis.","authors":"Yi-Jin Wu, Yan-Rong Yang, Ya-Ling Yan, Han-Yinan Yang, Jun-Rong Du","doi":"10.1007/s11010-025-05297-w","DOIUrl":"10.1007/s11010-025-05297-w","url":null,"abstract":"<p><p>The incidence and hospitalization rate of kidney disease, especially end-stage renal disease, have increased significantly, which seriously endangers the health of patients. Mitochondria are the core organelles of cellular energy metabolism, and their dysfunction can lead to kidney energy supply insufficiency and oxidative stress damage, which has become a global public health problem. Studies have shown that the disturbance of mitochondrial quality control mechanisms, including mitochondrial dynamics, autophagy, oxidative stress regulation and biosynthesis, is closely related to the occurrence and development of renal fibrosis (RF). As a multicellular pathological process, RF involves the injury and shedding of podocytes, the transdifferentiation of renal tubular epithelial cells, the activation of fibroblasts, and the infiltration of macrophages, among which the mitochondrial dysfunction plays an important role. This review systematically elaborates the molecular mechanisms of mitochondrial damage during RF progression, aiming to provide theoretical foundations for developing novel therapeutic strategies to delay RF advancement.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4889-4906"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.","authors":"Limei Chen, Zhihui Wu, Weixi Yuan, Nan Chen, Peina Lin, Senyi Liao, Guopeng Xie","doi":"10.1007/s11010-025-05316-w","DOIUrl":"10.1007/s11010-025-05316-w","url":null,"abstract":"<p><p>Advancements in tumor research have highlighted the potential of epigenetic therapies as a targeted approach to cancer treatment. However, the application of these therapies has faced challenges due to the issue of substrate availability since the discovery of epigenetic modifications. Interestingly, metabolic changes are closely associated with epigenetic changes, and notably, certain metabolic enzymes exhibit nuclear localization within epigenetically active cellular contexts. This suggests that nuclear localization of metabolic enzymes may provide a mechanistic foundation for addressing substrate availability issues in epigenetic regulation. To date, there has been limited progress in synthesizing this information systematically. In this study, we provide an overview of the interplay between metabolic enzymes and epigenetic mechanisms, highlighting their critical roles. Subsequently, we summarize recent advances regarding the nuclear localization of metabolic enzymes, shedding light on their emerging roles in epigenetic regulation and oncogenesis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5009-5028"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAPK signaling mediates tamoxifen resistance in estrogen receptor-positive breast cancer.","authors":"Sepide Javankiani, Soheil Bolandi, Anvar Soleimani, Mohammad Saeed Soleimani Meigoli, Mahdis Parsafar, Sadaf Safaei, Mojgan Esmailpour, Sogol Nadimi, Nahal Aghajamal Avval, Seyed Mohammad Ali Fazayel, Zahra Zahed, Malihe Sharafi","doi":"10.1007/s11010-025-05304-0","DOIUrl":"10.1007/s11010-025-05304-0","url":null,"abstract":"<p><p>Tamoxifen is a cornerstone in the treatment of estrogen receptor (ER)-positive breast cancer, yet resistance to this therapy remains a significant clinical challenge. In most cases, the resistance phenotype is not caused by loss or mutation of the ER, but by changes in multiple proliferative and survival pathways. The mitogen-activated protein kinase (MAPK) signaling pathways regulate various cellular processes such as cell growth, proliferation, and apoptosis. This review provides a comprehensive analysis of molecular mechanisms that sustain MAPK activation and promote tamoxifen resistance. We evaluated molecular factors that promote the survival of tamoxifen-resistant cells through the regulation of MAPK signaling, including growth factors, RNA-binding proteins, non-genomic ER variants, and microRNAs. Mitochondrial dynamics and their regulation by MAPK highlight novel adaptive mechanisms employed by resistant cells to survive. Furthermore, MAPK-mediated phosphorylation of ERα enhances resistance through ligand-independent activation and sustained cellular proliferation. MAPK and parallel oncogenic pathways, including PI3K/AKT and receptor tyrosine kinases (EGFR, IGF-1R, and FGFR), function synergistically to enhance signaling redundancy and compensatory survival mechanisms. Therapeutic interventions targeting MAPK signaling-ranging from small-molecule inhibitors to RNA-based therapies-offer promising avenues for overcoming tamoxifen resistance.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"4973-4989"},"PeriodicalIF":3.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}