International Journal of Molecular Sciences最新文献_第2页

Oxidative Stress, Mitochondrial Quality Control, Autophagy, and Sirtuins in Heart Failure. 心力衰竭中的氧化应激、线粒体质量控制、自噬和Sirtuins。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199826

Jan Krekora, Marcin Derwich, Jarosław Drożdż, Elzbieta Pawlowska, Janusz Blasiak

{"title":"Oxidative Stress, Mitochondrial Quality Control, Autophagy, and Sirtuins in Heart Failure.","authors":"Jan Krekora, Marcin Derwich, Jarosław Drożdż, Elzbieta Pawlowska, Janusz Blasiak","doi":"10.3390/ijms26199826","DOIUrl":"10.3390/ijms26199826","url":null,"abstract":"Heart failure (HF) has become an emerging problem, especially in regions where life expectancy is increasing. Despite its prevalence, the mechanisms behind HF development are not well understood, which is reflected in the lack of curative therapies. Mitochondria, autophagy, and sirtuins form a crucial triad involved in HF pathogenesis, interconnected by oxidative stress. Identifying a common pathway involving these three components could be valuable in developing new treatment strategies. Since HF is the end result of several cardiovascular diseases, this review highlights the main HF precursors and explores the roles of mitochondrial quality control (mtQC), autophagy, and sirtuins in HF development. Dysfunctional mitochondria may play a key role by enhancing oxidative stress and influencing autophagy and sirtuins, both of which possess antioxidant properties. The dual nature of autophagy-its pro-life and pro-death roles-may contribute to different outcomes in HF related to oxidative stress. As mtQC, autophagy, and sirtuins may interact, we present data on their mutual dependencies in HF. However, the specificity of these interactions remains unclear and needs further investigation, which could help identify new therapeutic targets. In conclusion, the interplay between mtQC, autophagy, and sirtuins may be crucial in HF pathogenesis and could be leveraged in developing HF treatments.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum Metabolomics Uncovers Immune and Lipid Pathway Alterations in Lambs Supplemented with Novel LAB-Bifidobacterium Cocktail. 血清代谢组学揭示了添加新型实验室双歧杆菌鸡尾酒后羔羊免疫和脂质途径的改变。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199808

Roman Wójcik, Angelika Król-Grzymała, Dawid Tobolski, Assel Paritova, Estefanía García-Calvo, Jan Miciński, Grzegorz Zwierzchowski

{"title":"Serum Metabolomics Uncovers Immune and Lipid Pathway Alterations in Lambs Supplemented with Novel LAB-Bifidobacterium Cocktail.","authors":"Roman Wójcik, Angelika Król-Grzymała, Dawid Tobolski, Assel Paritova, Estefanía García-Calvo, Jan Miciński, Grzegorz Zwierzchowski","doi":"10.3390/ijms26199808","DOIUrl":"10.3390/ijms26199808","url":null,"abstract":"The ban on antibiotic growth promoters in livestock has intensified the search for effective probiotic alternatives. This study assessed the impact of a novel probiotic cocktail-comprising Lactobacillus plantarum AMT14 and AMT4, L. rhamnosus AMT15, and Bifidobacterium animalis AMT30-on the serum metabolome of lambs using an untargeted GC/MS approach. Sixteen Kamieniec lambs were divided into control and probiotic groups, with serum collected on days 0, 15, and 30. Metabolomic profiling revealed significant alterations in lipid and amino acid metabolism in the probiotic group. By day 15, 38 metabolites were upregulated, including 9,12-octadecadienoic acid, arachidonic acid, and cholesterol. On day 30, key increases included D-glucose, oleic acid, glycine, decanoic acid, and L-leucine. Multivariate analyses (PCA, PLS-DA) demonstrated clear separation between groups, and ROC analysis identified strong biomarkers with high predictive accuracy. These results suggest that probiotic supplementation can beneficially modulate host metabolism, potentially enhancing immune and physiological function in lambs. This highlights the value of multi-strain LAB-Bifidobacterium probiotics as a promising strategy for improving health and reducing antibiotic reliance in ruminant production systems.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Viral Metagenomic Next-Generation Sequencing for One Health Discovery and Surveillance of (Re)Emerging Viruses: A Deep Review. 新一代病毒宏基因组测序用于健康发现和（再）新发病毒监测：深入综述。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199831

Tristan Russell, Elisa Formiconi, Mícheál Casey, Maíre McElroy, Patrick W G Mallon, Virginie W Gautier

{"title":"Viral Metagenomic Next-Generation Sequencing for One Health Discovery and Surveillance of (Re)Emerging Viruses: A Deep Review.","authors":"Tristan Russell, Elisa Formiconi, Mícheál Casey, Maíre McElroy, Patrick W G Mallon, Virginie W Gautier","doi":"10.3390/ijms26199831","DOIUrl":"10.3390/ijms26199831","url":null,"abstract":"Viral metagenomic next-generation sequencing (vmNGS) has transformed our capacity for the untargeted detection and characterisation of (re)emerging zoonotic viruses, surpassing the limitations of traditional targeted diagnostics. In this review, we critically evaluate the current landscape of vmNGS, highlighting its integration within the One Health paradigm and its application to the surveillance and discovery of (re)emerging viruses at the human-animal-environment interface. We provide a detailed overview of vmNGS workflows including sample selection, nucleic acid extraction, host depletion, virus enrichment, sequencing platforms, and bioinformatic pipelines, all tailored to maximise sensitivity and specificity for diverse sample types. Through selected case studies, including SARS-CoV-2, mpox, Zika virus, and a novel henipavirus, we illustrate the impact of vmNGS in outbreak detection, genomic surveillance, molecular epidemiology, and the development of diagnostics and vaccines. The review further examines the relative strengths and limitations of vmNGS in both passive and active surveillance, addressing barriers such as cost, infrastructure requirements, and the need for interdisciplinary collaboration. By integrating molecular, ecological, and public health perspectives, vmNGS stands as a central tool for early warning, comprehensive monitoring, and informed intervention against (re)emerging viral threats, underscoring its critical role in global pandemic preparedness and zoonotic disease control.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diverse Members of the Phylum Armatimonadota Promote the Growth of Aquatic Plants, Duckweeds. 水草门的不同成员促进水生植物，浮萍的生长。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199824

Tomoki Iwashita, Ayaka Makino, Ryosuke Nakai, Yasuko Yoneda, Yoichi Kamagata, Tadashi Toyama, Kazuhiro Mori, Yasuhiro Tanaka, Hideyuki Tamaki

{"title":"Diverse Members of the Phylum Armatimonadota Promote the Growth of Aquatic Plants, Duckweeds.","authors":"Tomoki Iwashita, Ayaka Makino, Ryosuke Nakai, Yasuko Yoneda, Yoichi Kamagata, Tadashi Toyama, Kazuhiro Mori, Yasuhiro Tanaka, Hideyuki Tamaki","doi":"10.3390/ijms26199824","DOIUrl":"10.3390/ijms26199824","url":null,"abstract":"Duckweeds are small, fast-growing aquatic plants with high starch and protein content, making them promising candidates for next-generation plant biomass resources. Despite their importance, little is known about their interactions with microorganisms, particularly plant growth-promoting bacteria (PGPB), which play key roles in enhancing plant productivity. In this study, we report the plant growth-promoting effects of strain LA-C6, a member of the phylum Armatimonadota, isolated from duckweed fronds. Based on 16S rRNA gene analysis, this strain represents a novel genus-level lineage, and is referred to as Fimbriimonadaceae bacterium strain LA-C6. In axenic co-culture experiments, strain LA-C6 promoted duckweed growth, increasing the frond proliferation of four duckweed species (Lemna minor, Lemna aequinoctialis, Spirodela polyrhiza, and Landoltia punctata) by 1.8- to 4.0-fold compared with uninoculated controls. Importantly, three other phylogenetically distinct Armatimonadota species also exhibited significant plant growth-promoting effects on L. minor, increasing frond number by up to 2.3-fold and dry weight by up to 2.4-fold. This finding highlights the broader potential of diverse Armatimonadota members as PGP bacteria. A survey of the IMNGS database showed that strain LA-C6 and other Armatimonadota species are widely distributed across diverse plant-associated environments. Biochemical assays and gene prediction analyses revealed that strain LA-C6 produces indole-3-acetic acid (IAA) as a representative PGP trait, whereas no additional PGP-associated traits were detected. These results suggest that diverse bacterial lineages within the phylum Armatimonadota exert growth-promoting effects on aquatic plants, potentially through yet-to-be-identified mechanisms.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipid Biomarkers in Glioma: Unveiling Molecular Heterogeneity Through Tissue and Plasma Profiling. 胶质瘤中的脂质生物标志物：通过组织和血浆分析揭示分子异质性。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199820

Khairunnisa Abdul Rashid, Norlisah Ramli, Kamariah Ibrahim, Vairavan Narayanan, Jeannie Hsiu Ding Wong

{"title":"Lipid Biomarkers in Glioma: Unveiling Molecular Heterogeneity Through Tissue and Plasma Profiling.","authors":"Khairunnisa Abdul Rashid, Norlisah Ramli, Kamariah Ibrahim, Vairavan Narayanan, Jeannie Hsiu Ding Wong","doi":"10.3390/ijms26199820","DOIUrl":"10.3390/ijms26199820","url":null,"abstract":"Gliomas are aggressive brain tumours with diverse histological and molecular features, complicating accurate diagnosis and treatment. Dysregulated lipid metabolism contributes to glioma progression, and analysing lipid profiles in plasma and tissue may enhance diagnostic and prognostic accuracy. This study investigated lipid dysregulation to identify key lipid signatures that distinguish glioma from other brain diseases and examined the associations between lipid biomarkers in glioma tissue and plasma. Biospecimens from 11 controls and 72 glioma patients of varying grades underwent lipidomic profiling using liquid chromatography-mass spectrometry. Univariate and multivariate analyses identified differentially abundant lipids, and correlation analysis evaluated the associations between tissue and plasma biomarkers. Lipidomic analysis revealed distinct lipid profiles in the tissues and plasma of glioma patients compared to those of controls. Prominent lipid metabolites in glioma tissues included LPC 21:3 (AUC = 0.925), DG 43:11 (AUC = 0.906), and PC 33:1 (AUC = 0.892), which served as effective biomarkers. Conversely, in plasma, lipid metabolites such as phosphatidylethanolamine (PE 21:3, AUC = 0.862), ceramide-1-phosphate (CerP 26:1, AUC = 0.861), and sphingomyelin (SM 24:3, AUC = 0.858) were identified as the most promising lipid biomarkers. Significant positive and negative correlations were observed between the tissue and plasma lipid biomarkers of glioma patients. Lipidomic profiling revealed aberrant lipid classes and pathways in glioma tissues and plasma, enhancing understanding of glioma heterogeneity and potential clinical applications.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methods for Assessing MAGL Enzymatic Activity: An Extensive Review of Past and Emerging Approaches. 评估MAGL酶活性的方法：对过去和新兴方法的广泛回顾。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199829

Giulia Bononi, Eva Landucci, Miriana Di Stefano, Lisa Piazza, Simone Bertini, Marco Macchia, Carlotta Granchi

{"title":"Methods for Assessing MAGL Enzymatic Activity: An Extensive Review of Past and Emerging Approaches.","authors":"Giulia Bononi, Eva Landucci, Miriana Di Stefano, Lisa Piazza, Simone Bertini, Marco Macchia, Carlotta Granchi","doi":"10.3390/ijms26199829","DOIUrl":"10.3390/ijms26199829","url":null,"abstract":"Monoacylglycerol lipase (MAGL) is a key serine hydrolase involved in lipid metabolism, catalyzing the hydrolysis of monoacylglycerols into free fatty acids and glycerol. MAGL plays a central role in regulating endocannabinoid signaling and lipid homeostasis, processes often dysregulated in cancer and other pathological conditions. In recent years, MAGL has emerged as a promising therapeutic target, particularly in oncology, where its inhibition has shown potential to impair tumor growth, metastasis, and inflammation-driven processes. Alongside the development of selective MAGL inhibitors, several biochemical methods have been established to measure MAGL enzymatic activity, providing essential tools for target validation and inhibitor characterization. In this review, we provide a comprehensive and critical overview of the main approaches developed for MAGL activity evaluation, including radiometric, chromatographic, colorimetric, fluorescence-based, bioluminescence-based, and activity-based protein profiling (ABPP) assays. For each method, we discuss principles, advantages, and limitations. This review aims to support researchers in the selection of the most appropriate assay strategy for their experimental needs, ultimately fostering the rapid and accurate development of novel MAGL inhibitors with potential applications in cancer therapy and metabolic disease management.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of α-L-Rhamnosidase and β-D-Glucosidase Subunits of Naringinase Immobilized on a Magnetic Polysaccharide Carrier. 磁性多糖载体固定化柚皮苷酶α- l -鼠李糖苷酶和β- d -葡萄糖苷酶亚基的研究

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199813

Joanna Bodakowska-Boczniewicz, Zbigniew Garncarek

{"title":"Characterization of α-L-Rhamnosidase and β-D-Glucosidase Subunits of Naringinase Immobilized on a Magnetic Polysaccharide Carrier.","authors":"Joanna Bodakowska-Boczniewicz, Zbigniew Garncarek","doi":"10.3390/ijms26199813","DOIUrl":"10.3390/ijms26199813","url":null,"abstract":"Naringinase consists of two enzymes: α-L-rhamnosidase and β-D-glucosidase. The enzyme was immobilized on a carrier prepared from carob gum activated with polyethyleneimine. Cross-linking with dextran aldehyde was used to improve the stability of the immobilization. Knowledge of the characteristics of naringinase subunits is important for developing efficient and selective enzymatic reactions involving flavonoids. This study aimed to characterize two subunits of naringinase-α-L-rhamnosidase and β-D-glucosidase-free, immobilized on a magnetic polysaccharide carrier and cross-linked with dextran aldehyde. The characterization of free, immobilized, and stabilized naringinase, as well as α-L-rhamnosidase and β-D-glucosidase, included the effect of pH and temperature on enzyme activity, as well as the determination of their stability depending on the pH and temperature of the environment, and the determination of kinetic constants. Immobilization and subsequent stabilization of naringinase did not affect the optimal pH for the activity of α-L-rhamnosidase and β-D-glucosidase. Immobilization caused a change in the optimal temperature for the activity of α-L-rhamnosidase and β-D-glucosidase from 60 to 65°. Cross-linking of immobilized naringinase with dextran aldehyde increased the temperature stability of its subunits. Cross-linking also altered the pH stability profile of β-D-glucosidase. Immobilization and stabilization of naringinase slightly reduced the maximum reaction rate for α-L-rhamnosidase and β-D-glucosidase compared to the free enzyme. As a result of immobilization, the enzymes' affinity for substrates for both subunits decreased.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exposure to Fluoride During Pregnancy and Lactation Induces Metabolic Imbalance in Pancreas: A Toxicological Insight Using the Rat Model. 妊娠期和哺乳期接触氟化物诱导胰腺代谢失衡：大鼠模型毒理学研究

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199817

Marta Skórka-Majewicz, Wojciech Żwierełło, Arleta Drozd, Irena Baranowska-Bosiacka, Donata Simińska, Agata Wszołek, Izabela Gutowska

{"title":"Exposure to Fluoride During Pregnancy and Lactation Induces Metabolic Imbalance in Pancreas: A Toxicological Insight Using the Rat Model.","authors":"Marta Skórka-Majewicz, Wojciech Żwierełło, Arleta Drozd, Irena Baranowska-Bosiacka, Donata Simińska, Agata Wszołek, Izabela Gutowska","doi":"10.3390/ijms26199817","DOIUrl":"10.3390/ijms26199817","url":null,"abstract":"Fluoride is a widespread environmental toxin that disrupts metabolic and endocrine functions, but its impact on pancreatic inflammation and hormone secretion remains unclear. This study examined how chronic fluoride exposure affects pancreatic inflammation and secretory function in rats. Pregnant Wistar rats received sodium fluoride (NaF) at 50 mg/L in drinking water during gestation and lactation. Male offspring continued exposure until 3 months old. Controls received fluoride-free water. Pancreatic tissue and serum were collected. Fluoride levels were measured potentiometrically. Eicosanoids were quantified by SPE and HPLC. Serum insulin, glucagon, and somatostatin were measured by ELISA. Histological and biochemical markers of inflammation and oxidative stress were assessed. Fluoride exposure did not lead to significant accumulation in the pancreas or serum. However, fluoride-exposed rats exhibited a significant decrease in serum insulin and somatostatin concentrations, while glucagon levels remained unchanged. Additionally, the pancreas of fluoride-treated animals showed markedly elevated levels of pro-inflammatory eicosanoids, including prostaglandin E2, leukotrienes A4 and B4, and HETE/HODE derivatives, indicating activation of cyclooxygenase and lipoxygenase pathways. Sustained low-dose fluoride exposure induced pancreatic inflammation and disrupted endocrine homeostasis in rats. These findings suggest that chronic fluoride intake may impair insulin secretion and promote pre-diabetic alterations, warranting further research.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The SGLT2 Inhibitor Dapagliflozin Disrupts the Cell Cycle at High Concentrations Without Altering Glycosphingolipid (De Novo)Biosynthesis. SGLT2抑制剂Dapagliflozin在高浓度下破坏细胞周期而不改变鞘糖脂（De Novo）生物合成。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199811

Richard Jennemann, Roger Sandhoff

{"title":"The SGLT2 Inhibitor Dapagliflozin Disrupts the Cell Cycle at High Concentrations Without Altering Glycosphingolipid (De Novo)Biosynthesis.","authors":"Richard Jennemann, Roger Sandhoff","doi":"10.3390/ijms26199811","DOIUrl":"10.3390/ijms26199811","url":null,"abstract":"Modern computational screening methods are valuable tools for repurposing approved drugs for novel therapeutic applications. They provide initial insights into alternative uses and may significantly shorten the lengthy process of drug development and regulatory approval. Treatment options for glycosphingolipidoses, lysosomal storage diseases involving glycosphingolipids (GSLs), are currently limited to a few drugs that inhibit de novo GSL biosynthesis, such as eliglustat and miglustat (Zavesca®). In the search for alternative drugs, dapagliflozin emerged as a promising candidate for off-target therapy. In the present study, we investigated whether dapagliflozin can indeed inhibit GSL synthesis, as predicted by previous computational analyses, and compared its effects with those of the glycosphingolipid synthesis inhibitor, the eliglustat analog Genz-123346, in murine 3T3 and Hepa 1-6 cell lines. While Genz-123346 significantly inhibited glycosphingolipid biosynthesis at concentrations as low as 1 µM, dapagliflozin, even up to 50 µM, had no effect on biosynthesis or de novo biosynthesis in either cell line. These results indicate that dapagliflozin, although assessing effects on the cell cycle, including proliferation at high concentrations, is not a suitable candidate for treating glycosphingolipid storage diseases by substrate reduction.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Special Issue "Skeletal Muscle Adaptations to Oxidative Stress". 特刊“骨骼肌适应氧化应激”。

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2025-10-09 DOI: 10.3390/ijms26199809

Guglielmo Duranti

引用次数: 0