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Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-14 DOI: 10.3390/biom15030414
Shadi Bazzazzadehgan, Zia Shariat-Madar, Fakhri Mahdi
{"title":"Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM.","authors":"Shadi Bazzazzadehgan, Zia Shariat-Madar, Fakhri Mahdi","doi":"10.3390/biom15030414","DOIUrl":"10.3390/biom15030414","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) encompasses a range of clinical manifestations, with uncontrolled diabetes leading to progressive or irreversible damage to various organs. Numerous genes associated with monogenic diabetes, exhibiting classical patterns of inheritance (autosomal dominant or recessive), have been identified. Additionally, genes involved in complex diabetes, which interact with environmental factors to trigger the disease, have also been discovered. These genetic findings have raised hopes that genetic testing could enhance diagnostics, disease surveillance, treatment selection, and family counseling. However, the accurate interpretation of genetic data remains a significant challenge, as variants may not always be definitively classified as either benign or pathogenic. Research to date, however, indicates that periodic reevaluation of genetic variants in diabetes has led to more consistent findings, with biases being steadily eliminated. This has improved the interpretation of variants across diverse ethnicities. Clinical studies suggest that genetic risk information may motivate patients to adopt behaviors that promote the prevention or management of T2DM. Given that the clinical features of certain monogenic diabetes types overlap with T2DM, and considering the significant role of genetic variants in diabetes, healthcare providers caring for prediabetic patients should consider genetic testing as part of the diagnostic process. This review summarizes current knowledge of the most common genetic variants associated with T2DM, explores novel therapeutic targets, and discusses recent advancements in the pharmaceutical management of uncontrolled T2DM.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728254","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 Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-14 DOI: 10.3390/biom15030416
Shashwat Sharma, Matthew McKenzie
{"title":"The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency.","authors":"Shashwat Sharma, Matthew McKenzie","doi":"10.3390/biom15030416","DOIUrl":"10.3390/biom15030416","url":null,"abstract":"<p><p>Living systems require energy to maintain their existence and perform tasks such as cell division. This energy is stored in several molecular forms in nature, specifically lipids, carbohydrates, and amino acids. At a cellular level, energy is extracted from these complex molecules and transferred to adenosine triphosphate (ATP) in the cytoplasm and mitochondria. Within the mitochondria, fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are crucial metabolic processes involved in generating ATP, with defects in these pathways causing mitochondrial disease. Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a fatty acid β-oxidation disorder (FAOD) affecting 1 to 2 individuals per 100,000. Similar to other mitochondrial disorders, there is no cure for VLCADD, with symptomatic treatment comprising dietary management and supplementation with medium-chain fatty acids to bypass the enzyme deficiency. While this addresses the primary defect in VLCADD, there is growing evidence that other aspects of mitochondrial function are also affected in VLCADD, including secondary defects in OXPHOS function. Here, we review our current understanding of VLCADD with a focus on the associated biochemical and molecular defects that can disrupt multiple aspects of mitochondrial function. We describe the interactions between FAO proteins and the OXPHOS complexes and how these interactions are critical for maintaining the activity of both metabolic pathways. In particular, we describe what is now known about the protein-protein interactions between VLCAD and the OXPHOS supercomplex and how their disruption contributes to overall VLCADD pathogenesis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728327","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
Cold-Active Starch-Degrading Enzymes from a Cold and Alkaline Greenland Environment: Role of Ca2+ Ions and Conformational Dynamics in Psychrophilicity.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-14 DOI: 10.3390/biom15030415
Malthe Kjær Bendtsen, Jan Stanislaw Nowak, Pedro Paiva, Marcos López Hernández, Pedro Ferreira, Jan Skov Pedersen, Nicolai Sundgaard Bekker, Elia Viezzi, Francesco Bisiak, Ditlev E Brodersen, Lars Haastrup Pedersen, Athanasios Zervas, Pedro A Fernandes, Maria Joao Ramos, Peter Stougaard, Mariane Schmidt Thøgersen, Daniel E Otzen
{"title":"Cold-Active Starch-Degrading Enzymes from a Cold and Alkaline Greenland Environment: Role of Ca<sup>2+</sup> Ions and Conformational Dynamics in Psychrophilicity.","authors":"Malthe Kjær Bendtsen, Jan Stanislaw Nowak, Pedro Paiva, Marcos López Hernández, Pedro Ferreira, Jan Skov Pedersen, Nicolai Sundgaard Bekker, Elia Viezzi, Francesco Bisiak, Ditlev E Brodersen, Lars Haastrup Pedersen, Athanasios Zervas, Pedro A Fernandes, Maria Joao Ramos, Peter Stougaard, Mariane Schmidt Thøgersen, Daniel E Otzen","doi":"10.3390/biom15030415","DOIUrl":"10.3390/biom15030415","url":null,"abstract":"<p><p>Cold-active enzymes hold promise for energy-efficient processes. Amylases are widely used in household and industrial applications, but only a few are cold-active. Here we describe three novel secreted amylases, Rho13, Ika2 and I3C6, all from bacteria growing in the cold and alkaline ikaite columns in Greenland. They all hydrolyzed starch to smaller malto-oligomers, but only Rho13 and Ika2 hydrolyzed cyclodextrins, and only Ika2 displayed transglycosylation activity. Ika2 forms a stable dimer, while both Rho13 and I3C6 are mainly monomeric. They all have optimal active temperatures around 30-35 °C and significant enzymatic activity below 20 °C, but Rho13 and I3C6 had an alkaline optimal pH, while Ika2 was markedly acidophilic. They showed complex dependence on Ca<sup>2+</sup> concentration, with the activity of Rho13 and I3C6 following a bell-shaped curve and Ika2 being unaffected; however, removal of Ca<sup>2+</sup> reduced the stability of all three enzymes. Loss of structure occurred well above the temperature of optimal activity, showing the characteristic psychrophilic divorce between activity and stability. MD simulations showed that Ika2 did not have a well-defined Ca<sup>2+</sup> binding site, while Rho13 and I3C6 both maintained one stably bound Ca<sup>2+</sup> ion. We identified psychrophilic features as higher levels of backbone fluctuations compared to mesophilic counterparts, based on a lower number of internal hydrogen bonds and salt bridges. This increased fluctuation was also found in regions outside the active site and may provide easier substrate access and accommodation, as well as faster barrier transitions. Our work sheds further light on the many ways in which psychrophilic enzymes adapt to increased catalysis at lower temperatures.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727897","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
Region-Specific Impact of Repeated Synthetic Cannabinoid Exposure and Withdrawal on Endocannabinoid Signaling, Gliosis, and Inflammatory Markers in the Prefrontal Cortex and Hippocampus.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-14 DOI: 10.3390/biom15030417
Evelin Vadas, Antonio J López-Gambero, Antonio Vargas, Miguel Rodríguez-Pozo, Patricia Rivera, Juan Decara, Antonia Serrano, Stella Martín-de-Las-Heras, Fernando Rodríguez de Fonseca, Juan Suárez
{"title":"Region-Specific Impact of Repeated Synthetic Cannabinoid Exposure and Withdrawal on Endocannabinoid Signaling, Gliosis, and Inflammatory Markers in the Prefrontal Cortex and Hippocampus.","authors":"Evelin Vadas, Antonio J López-Gambero, Antonio Vargas, Miguel Rodríguez-Pozo, Patricia Rivera, Juan Decara, Antonia Serrano, Stella Martín-de-Las-Heras, Fernando Rodríguez de Fonseca, Juan Suárez","doi":"10.3390/biom15030417","DOIUrl":"10.3390/biom15030417","url":null,"abstract":"<p><p>Synthetic cannabinoid use raises concerns about its neuroinflammatory effects, including molecular adaptations of the endocannabinoid system (ECS) in the brain. This study investigates the pharmacological effects of 14-day repeated intraperitoneal administration, as well as 14-day administration followed by a 7-day withdrawal period of two synthetic cannabinoids: WIN55,212-2 and HU-210. The study assessed gene expression and protein markers related to the ECS, gliosis, and inflammation in two brain regions critical for cognitive processes and memory-key components of addiction pathways-the prefrontal cortex (PFC) and the hippocampus of rats. Our findings showed that repeated WIN55,212-2 administration induced adaptations in the ECS and reduced IBA1, a glial protein marker, along with inflammatory responses likely mediated through CB2 activity. Notably, regional differences emerged in the hippocampus, where repeated administration of WIN55,212-2 and HU-210 increased IBA1 and inflammatory markers, effects unrelated to CB2 activity. Withdrawal from WIN55,212-2 in the PFC, as well as from both compounds in the hippocampus, decreased IBA1 levels. This was associated with altered protein expression of cannabinoid-synthesizing and degrading enzymes, favoring acylethanolamide synthesis. These findings highlight region-specific effects of synthetic cannabinoids on cannabinoid signaling, gliosis, and inflammation. Further research is needed to elucidate the long-term neurobiological consequences of synthetic cannabinoid use and withdrawal.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728296","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
IL-6 Baseline Values and Dynamic Changes in Predicting Sepsis Mortality: A Systematic Review and Meta-Analysis.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-13 DOI: 10.3390/biom15030407
Norberth-Istvan Varga, Iulia Cristina Bagiu, Dan Dumitru Vulcanescu, Voichita Lazureanu, Mirela Turaiche, Ovidiu Rosca, Adrian Vasile Bota, Florin George Horhat
{"title":"IL-6 Baseline Values and Dynamic Changes in Predicting Sepsis Mortality: A Systematic Review and Meta-Analysis.","authors":"Norberth-Istvan Varga, Iulia Cristina Bagiu, Dan Dumitru Vulcanescu, Voichita Lazureanu, Mirela Turaiche, Ovidiu Rosca, Adrian Vasile Bota, Florin George Horhat","doi":"10.3390/biom15030407","DOIUrl":"10.3390/biom15030407","url":null,"abstract":"<p><p>Sepsis, a life-threatening condition arising from a dysregulated immune response to infection, is a significant health burden globally. Interleukin-6 (IL-6), an inflammatory cytokine produced by immune cells as a response to infection and tissue damage, plays a key role in the pathogenesis of sepsis. This systematic review and meta-analysis aimed to investigate the association of the baseline plasma levels of IL-6, and the dynamic change in these levels over a timespan of 96 h, with short-term mortality. A systematic literature search was conducted across multiple databases. Studies were included if they assessed the independent prognostic value of IL-6 in adult sepsis patients, used well-defined sepsis criteria, and reported at least one IL-6 measurement. Pooled effect estimates for the association between IL-6 and 28-30-day mortality were determined using logistic regression and AUROC analysis. Thirty-one studies, encompassing 4566 patients, were included. While baseline IL-6 levels and 96 h IL-6 clearance were not significantly associated with mortality risk (pooled OR 1.001, 95% CI 0.999-1.003 and 1.019, 95% CI 0.925-1.112, respectively), AUROC analysis indicated moderate-to-good discriminatory power for both baseline (0.701, 95% CI 0.660-0.742) and 96 h IL-6 clearance (0.828, 95% CI 0.736-0.919) in predicting 28-day mortality. While not a strong independent predictor, IL-6 demonstrates some discriminatory ability, suggesting its potential value in conjunction with other biomarkers.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728242","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
Weight Reduction with GLP-1 Agonists and Paths for Discontinuation While Maintaining Weight Loss.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-13 DOI: 10.3390/biom15030408
Allison B Reiss, Shelly Gulkarov, Raymond Lau, Stanislaw P Klek, Ankita Srivastava, Heather A Renna, Joshua De Leon
{"title":"Weight Reduction with GLP-1 Agonists and Paths for Discontinuation While Maintaining Weight Loss.","authors":"Allison B Reiss, Shelly Gulkarov, Raymond Lau, Stanislaw P Klek, Ankita Srivastava, Heather A Renna, Joshua De Leon","doi":"10.3390/biom15030408","DOIUrl":"10.3390/biom15030408","url":null,"abstract":"<p><p>Worldwide, nearly 40% of adults are overweight and 13% are obese. Health consequences of excess weight include cardiovascular diseases, type 2 diabetes, dyslipidemia, and increased mortality. Treating obesity is challenging and calorie restriction often leads to rebound weight gain. Treatments such as bariatric surgery create hesitancy among patients due to their invasiveness. GLP-1 medications have revolutionized weight loss and can reduce body weight in obese patients by between 15% and 25% on average after about 1 year. Their mode of action is to mimic the endogenous GLP-1, an intestinal hormone that regulates glucose metabolism and satiety. However, GLP-1 drugs carry known risks and, since their use for weight loss is recent, may carry unforeseen risks as well. They carry a boxed warning for people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Gastrointestinal adverse events (nausea, vomiting, diarrhea) are fairly common while pancreatitis and intestinal obstruction are rarer. There may be a loss of lean body mass as well as premature facial aging. A significant disadvantage of using these medications is the high rate of weight regain when they are discontinued. Achieving success with pharmacologic treatment and then weaning to avoid future negative effects would be ideal.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728344","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
Probiotics and Diet in Rosacea: Current Evidence and Future Perspectives.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-13 DOI: 10.3390/biom15030411
Marco Manfredini, Michele Barbieri, Margherita Milandri, Caterina Longo
{"title":"Probiotics and Diet in Rosacea: Current Evidence and Future Perspectives.","authors":"Marco Manfredini, Michele Barbieri, Margherita Milandri, Caterina Longo","doi":"10.3390/biom15030411","DOIUrl":"10.3390/biom15030411","url":null,"abstract":"<p><p>Rosacea is a common inflammatory skin disease, characterized by erythema, papules and pustules. The pathophysiology of rosacea remains unclear, but the complex interplay between environmental and genetic factors may act as a trigger to an abnormal innate immune response associated with a multifaceted neurovascular reaction. Increasing evidence suggests that the gut microbiota is significantly involved in the pathogenesis of rosacea, playing an important role in the inflammatory cutaneous response. Dysbiosis, small intestinal bacterial overgrowth, Helicobacter pylori infection and innate immune system dysregulation mutually contribute to the pathophysiology of rosacea, but more extensive future research is needed to better clarify their precise mechanisms of action. Many dietary triggers have been postulated for this disease; however, there is a lack of well-made and controlled studies able to undoubtedly demonstrate a causal relationship between rosacea and diet. We analyzed the available studies on the role of diet and gut microbiome in rosacea and the positive clinical effects reported by the current literature on probiotics, prebiotics, postbiotics and nutrients. Ultimately, this article improves our understanding of the gut-skin axis in rosacea, focusing on how probiotic supplementation and diet could improve the clinical management of patients affected by this common and debilitating disease.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728279","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
G-Quadruplex Conformational Switching for miR-155-3p Detection Using a Ligand-Based Fluorescence Approach.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-13 DOI: 10.3390/biom15030410
Pedro Lourenço, Carla Cruz
{"title":"G-Quadruplex Conformational Switching for miR-155-3p Detection Using a Ligand-Based Fluorescence Approach.","authors":"Pedro Lourenço, Carla Cruz","doi":"10.3390/biom15030410","DOIUrl":"10.3390/biom15030410","url":null,"abstract":"<p><p>MicroRNA-155-3p (miR-155-3p) is an important biomarker in various pathological conditions, including cancer, making the development of sensitive and specific detection methods crucial. Here, we present a molecular beacon (MB-G4) that underwent a conformational switch upon hybridization with miR-155-3p, enabling the formation of a G-quadruplex (G4) structure. This G4 was recognized by the fluorogenic ligand N-methyl mesoporphyrin IX (NMM), producing a fluorescence signal proportional to the target concentration, making it a new detection method. The conformational dynamics of MB-G4 were characterized through circular dichroism (CD) spectroscopy and native polyacrylamide gel electrophoresis (PAGE), confirming the transition from a hairpin structure to an RNA-DNA hybrid duplex that facilitated G4 formation. The optimization of the experimental conditions, including the potassium chloride (KCl) and NMM concentrations, ensured selective detection with minimal background signal. The detection limit (LOD) was determined to be 10.85 nM, using a linear fluorescence response curve, and the specificity studies demonstrated a clear distinction between miR-155-3p and miR-155-5p. Furthermore, MB-G4 was studied with total RNA extracted from the lung cancer cell line A549 to evaluate its detection in a more complex environment and was able to detect its target, validating its potential for biological sample analysis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728235","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 Osgin Gene Family: Underexplored Yet Essential Mediators of Oxidative Stress.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-13 DOI: 10.3390/biom15030409
Grace Hussey, Marcus Royster, Nivedha Vaidy, Michael Culkin, Margaret S Saha
{"title":"The <i>Osgin</i> Gene Family: Underexplored Yet Essential Mediators of Oxidative Stress.","authors":"Grace Hussey, Marcus Royster, Nivedha Vaidy, Michael Culkin, Margaret S Saha","doi":"10.3390/biom15030409","DOIUrl":"10.3390/biom15030409","url":null,"abstract":"<p><p>The <i>Osgin</i> gene family consists of two members, <i>Osgin1</i> and <i>Osgin2</i>, involved in the cellular oxidative stress response. While many members of this essential cellular pathway have been extensively characterized, the <i>Osgin</i> gene family, despite its broad phylogenetic distribution, has received far less attention. Here, we review published articles and open-source databases to synthesize the current research on the evolutionary history, structure, biochemical and physiological functions, expression patterns, and role in disease of the <i>Osgin</i> gene family. Although <i>Osgin</i> displays broad spatiotemporal expression during development and adulthood, there is ambiguity regarding the cellular functions of the OSGIN proteins. A recent study identified OSGIN-1 as a flavin-dependent monooxygenase, but the biochemical role of OSGIN-2 has not yet been defined. Moreover, while the <i>Osgin</i> genes are implicated as mediators of cell proliferation, apoptosis, and autophagy, these functions have not been connected to the enzymatic classification of OSGIN. Misregulation of <i>Osgin</i> expression has long been associated with various disease states, yet recent analyses highlight the mechanistic role of OSGIN in pathogenesis and disease progression, underscoring the therapeutic potential of targeting OSGIN. In light of these findings, we suggest further avenues of research to advance our understanding of this essential, yet underexplored, gene family.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727875","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
GramSeq-DTA: A Grammar-Based Drug-Target Affinity Prediction Approach Fusing Gene Expression Information.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-12 DOI: 10.3390/biom15030405
Kusal Debnath, Pratip Rana, Preetam Ghosh
{"title":"GramSeq-DTA: A Grammar-Based Drug-Target Affinity Prediction Approach Fusing Gene Expression Information.","authors":"Kusal Debnath, Pratip Rana, Preetam Ghosh","doi":"10.3390/biom15030405","DOIUrl":"10.3390/biom15030405","url":null,"abstract":"<p><p>Drug-target affinity (DTA) prediction is a critical aspect of drug discovery. The meaningful representation of drugs and targets is crucial for accurate prediction. Using 1D string-based representations for drugs and targets is a common approach that has demonstrated good results in drug-target affinity prediction. However, these approach lacks information on the relative position of the atoms and bonds. To address this limitation, graph-based representations have been used to some extent. However, solely considering the structural aspect of drugs and targets may be insufficient for accurate DTA prediction. Integrating the functional aspect of these drugs at the genetic level can enhance the prediction capability of the models. To fill this gap, we propose GramSeq-DTA, which integrates chemical perturbation information with the structural information of drugs and targets. We applied a Grammar Variational Autoencoder (GVAE) for drug feature extraction and utilized two different approaches for protein feature extraction as follows: a Convolutional Neural Network (CNN) and a Recurrent Neural Network (RNN). The chemical perturbation data are obtained from the L1000 project, which provides information on the up-regulation and down-regulation of genes caused by selected drugs. This chemical perturbation information is processed, and a compact dataset is prepared, serving as the functional feature set of the drugs. By integrating the drug, gene, and target features in the model, our approach outperforms the current state-of-the-art DTA prediction models when validated on widely used DTA datasets (BindingDB, Davis, and KIBA). This work provides a novel and practical approach to DTA prediction by merging the structural and functional aspects of biological entities, and it encourages further research in multi-modal DTA prediction.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728236","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
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