International Journal of Molecular Sciences最新文献

{"title":"Improving Poly(3-Hydroxybutyrate) Properties Using Nanocellulose in Biomedical Applications: Thermal, Mechanical and Biological Studies.","authors":"Karolina Maternia-Dudzik, Łukasz Ożóg, Zuzanna Bober, Rafał Oliwa, Mariusz Oleksy, Angelika Kamizela, Agnieszka Szyszkowska, Katarzyna Rafińska, Weronika Gonciarz, Kamil Gancarczyk, Anna Czerniecka-Kubicka","doi":"10.3390/ijms26199795","DOIUrl":"10.3390/ijms26199795","url":null,"abstract":"<p><p>Poly(3-hydroxybutyrate), P3HB, is a biodegradable polymer produced and stored by different bacterial strains, including <i>Ralstonia eutropha H16.</i> P3HB was used to prepare biocompatible composites modified by nanocellulose. This study aimed to assess selected thermal, mechanical, and biological properties of the obtained nanobiocomposites. Thermal properties, as determined by differential scanning calorimetry measurements, were established. The crystallinity of nanocomposites and polymeric matrix was investigated using DSC analyses. The morphology of the nanocomposites was evaluated using scanning electron microscopy. The Food and Drug Administration and the European Medicines Agency confirmed the immunosafety of the tested nanocomposites and noted they had either no or very low levels of endotoxin contamination. Some mechanical properties of the investigated materials were also measured and are presented here. It was estimated that the addition of 1% by mass of nanocrystalline cellulose to P3HB causes the greatest improvement in the plasticization of the material, characterised by the best processing and utility properties. The processing window of nanobiocomposites was extended by approximately 25 °C in reference to the unfilled poly(3-hydroxybutyrate). Mechanical and thermal tests revealed that the most desirable properties oscillate around the addition of 0.5% and 1% nanocrystalline cellulose by mass in the nanobiocomposites. Biological studies on implant applications have shown that the addition of only 0.5% nanofiller to a nanobiocomposite can be of key importance.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300176","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":"Functional and Evolutionary Role of Reproductive Hormonal Dysregulation Following Dietary Exposure to Singed Meat.","authors":"Prosper Manu Abdulai, Orish Ebere Orisakwe, Costantino Parisi, Rubina Vangone, Corrado Pane, Emidio M Sivieri, Domenico Pirozzi, Giulia Guerriero","doi":"10.3390/ijms26199774","DOIUrl":"10.3390/ijms26199774","url":null,"abstract":"<p><p>Consumption of meat singed with non-standard fuels is a common practice in many low- and middle-income settings, yet it may introduce combustion-derived toxicants with serious health consequences. While the toxicological effects of pollutants such as polycyclic aromatic hydrocarbons and heavy metals are well documented, the specific impact of singed meat consumption on endocrine regulation remains poorly understood. Of particular concern is the reproductive hormonal network, which not only serves as a sensitive biomarker of systemic disruption but also represents an evolutionary safeguard of fertility and generational continuity. Our study addresses this knowledge gap using male Wistar rats fed for 90 days (week 0 to week 12) on diets containing increasing proportions (25%, 50%, 75%) of meat singed with firewood, liquefied petroleum gas (LPG), or tyres. Firewood- and tyre-singed meat induced dose- and source-dependent toxicity, including hepatocellular injury, impaired protein metabolism, elevated blood urea nitrogen and creatinine, organ hypertrophy, and pronounced oxidative stress. Hormonal analysis revealed reduced testosterone alongside increased FSH, LH, and prolactin, indicating hypothalamic-pituitary-gonadal axis disruption and reproductive risk. In contrast, LPG-singed meat caused only minor alterations. These findings highlight reproductive hormones as sensitive biomarkers, underscoring the health risks of singeing practices and their evolutionary implications for fertility and population fitness.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300364","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":"Adipocyte-Tumor Interactions in the Bone Marrow Niche: Implications for Metastasis and Therapy.","authors":"Alhomam Dabaliz, Mohammad Nawar Al Hakawati, Najmuddeen Alrashdan, Sarah Alrashdan, Mohamad Bakir, Khalid S Mohammad","doi":"10.3390/ijms26199781","DOIUrl":"10.3390/ijms26199781","url":null,"abstract":"<p><p>Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidative phosphorylation; the secretion of adipokines such as leptin and IL-6, which promote epithelial-to-mesenchymal transition, invasion, and immune evasion; regulation of osteoclastogenesis via RANKL expression; and the release of extracellular vesicles that reprogram cancer cell metabolism. Clinical and experimental studies show that BMA expansion correlates with increased tumor burden and poorer outcomes in breast, prostate, lung cancers, and multiple myeloma. Additionally, BMAs actively promote therapeutic resistance through metabolic rewiring and drug sequestration. Experimental models, ranging from in vitro co-cultures to in vivo patient-derived xenografts, demonstrate the complex roles of BMAs and also reveal important translational gaps. Despite promising preclinical approaches such as metabolic inhibitors, PPARγ modulation, adipokine blockade, and lifestyle changes, no therapies directly targeting BMAs have yet reached clinical practice. This review compiles current evidence on the biology of BMAs, their tumor-promoting interactions, and potential therapeutic strategies, while also highlighting unresolved questions about BMA heterogeneity, lipid flux, and immunometabolic crosstalk. By revealing how bone marrow adipocytes actively shape the metastatic niche through metabolic, endocrine, and immunological pathways, this review highlights their potential as novel biomarkers and therapeutic targets for improving the management of bone metastases.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300211","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":"Effects of the Polar Fraction of <i>Lophocereus schottii</i> on Gene Expression and Hepatocyte Proliferation in a Wistar Rat Model of Hepatocellular Carcinoma.","authors":"Marina Campos-Valdez, Jaime Sánchez-Meza, Arturo Orozco-Barocio, José A Domínguez-Rosales, Juliana Marisol Godínez-Rubí, Sarai C Rodríguez-Reyes, Erika Martínez-López, Miriam R Bueno-Topete, Manuel A Castro-García, Guillermo M Zúñiga-González, Daniel Ortuño-Sahagún, Laura V Sánchez-Orozco","doi":"10.3390/ijms26199788","DOIUrl":"10.3390/ijms26199788","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a major global health problem for which there are few effective treatments. Phytochemicals from natural sources, such as those found in cacti, exhibit chemoprotective and hepatoprotective properties. In this study, the effect of the polar fraction of <i>Lophocereus schottii</i> (LsPF) was investigated in a Wistar rat model of HCC induced by weekly administration of diethylnitrosamine (DEN, 50 mg/kg, i.p.) and 2-acetylaminofluorene (2-AAF, 25 mg/kg, i.g.) for 13 weeks. LsPF (50 mg/kg, i.g., three times per week) was administered either concurrently with HCC induction beginning in the first week or after seven weeks of HCC induction. LsPF did not lead to a significant improvement in macroscopic, biochemical or histologic results. However, when LsPF was administered after 7 weeks of HCC induction, it modulated the expression of genes related to liver carcinogenesis, including <i>SOD</i>, <i>CAT</i>, <i>CYP2E1</i>, <i>TGFB1</i>, <i>AFP</i>, and <i>COL1A.</i> In addition, co-administration of LsPF along with the damage treatment decreased the number of mitotic hepatocytes. These results suggest that LsPF can modulate gene expression and hepatocyte proliferation in HCC, with efficacy depending on the timing of administration, disease stage, and administration method. Further studies are needed to optimize its therapeutic potential.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300337","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":"Synthesis of New Phenothiazine/3-cyanoquinoline and Phenothiazine/3-aminothieno[2,3-b]pyridine(-quinoline) Heterodimers.","authors":"Victor V Dotsenko, Vladislav K Kindop, Vyacheslav K Kindop, Eva S Daus, Igor V Yudaev, Yuliia V Daus, Alexander V Bespalov, Dmitrii S Buryi, Darya Yu Lukina, Nicolai A Aksenov, Inna V Aksenova","doi":"10.3390/ijms26199798","DOIUrl":"10.3390/ijms26199798","url":null,"abstract":"<p><p>The aim of this work was to prepare new heterodimeric molecules containing pharmacophoric fragments of 3-cyanoquinoline/3-aminothieno[2,3-b]pyridine/3-aminothieno[2,3-b]quinoline on one side and phenothiazine on the other. The products were synthesized via selective S-alkylation of readily available 2-thioxo-3-cyanopyridines or -quinolines with N-(chloroacetyl)phenothiazines, followed by base-promoted Thorpe-Ziegler isomerization of the resulting N-[(3-cyanopyridin-2-ylthio)acetyl]phenothiazines. We found that both the S-alkylation and the Thorpe-Ziegler cyclization reactions, when conducted with KOH under heating, were accompanied to a significant extent by a side reaction involving the elimination of phenothiazine. Optimization of the conditions (0-5 °C, anhydrous N,N-dimethylacetamide and NaH or <i>t-</i>BuONa as non-nucleophilic bases) minimized the side reaction and increased the yields of the target heterodimers. The structures of the products were confirmed by IR spectroscopy, ¹H, and ¹³C DEPTQ NMR studies. It was demonstrated that the synthesized 3-aminothieno[2,3-b]pyridines can be acylated with chloroacetyl chloride in hot chloroform. The resulting chloroacetamide derivative reacts with potassium thiocyanate in DMF to form the corresponding 2-iminothiazolidin-4-one; in this process, phenothiazine elimination does not occur, and the Gruner-Gewald rearrangement product was not observed. The structural features and spectral characteristics of the synthesized 2-iminothiazolidin-4-one derivative were investigated by quantum chemical methods at the B3LYP-D4/def2-TZVP level. A range of drug-relevant properties was also evaluated using in silico methods, and ADMET parameters were calculated. A molecular docking study identified a number of potential protein targets for the new heterodimers, indicating the promise of these compounds for the development of novel antitumor agents.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300547","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":"MicroRNAs in Takotsubo Syndrome: A Systematic Review of Regulatory Networks in Stress-Induced Cardiomyopathy.","authors":"Domingos Sousa, Filipa Abreu Martins, Ângelo Luís, Pedro Serralheiro","doi":"10.3390/ijms26199790","DOIUrl":"10.3390/ijms26199790","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression and have been implicated in various physiological and pathological processes, including cardiovascular diseases. The clinical presentation, diagnostic criteria, and proposed pathophysiological mechanisms of Takotsubo Syndrome (TTS) are discussed, with an emphasis on the emerging evidence implicating miRNAs in its etiology and progression. A systematic review following the PRISMA guidelines was performed on the evidence regarding the interplay between miRNAs and TTS. A search of the Pubmed, Web of Science, and Scopus databases was conducted and resulted in 584 articles. Of these, 14 full-text articles were eligible for inclusion in the qualitative analysis. The reviewed studies suggest that multiple miRNAs are involved in the processes associated with TTS pathophysiology, including acute and chronic myocardial inflammation, oxidative stress, apoptosis, microvascular dysfunction, hypertrophy, and, ultimately, maladaptive cardiac remodelling. This review provides an overview of the current understanding of miRNAs in cardiovascular pathophysiology, with a specific focus on their potential roles in TTS. To the best of our knowledge, this is the first systematic exploration of the miRNAs involved in TTS and its modulation as potential biomarkers or therapeutic targets.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300180","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":"NRDE2 Interacts with an Early Transcription Elongation Complex and Widely Impacts Gene Expression.","authors":"Marina Srbic, Chaïmaa Belhaouari, Raoul Raffel, Laurine Lemaire, Jerome Barbier, Julie Bossuyt, Charbel Akkawi, Xavier Contreras, Rosemary Kiernan","doi":"10.3390/ijms26199792","DOIUrl":"10.3390/ijms26199792","url":null,"abstract":"<p><p>NRDE2 is a highly conserved protein implicated in post-transcriptional gene silencing in <i>Schizosaccharomyces pombe</i> and <i>Caenorhabditis elegans</i> and has been shown to modulate splicing in mammals. To explore whether NRDE2 participates in additional processes in human cells, we performed tandem affinity purification followed by proteomic analysis of NRDE2 from nuclear extracts of HEK293T and HeLa cells. Our analysis confirmed the interaction of NRDE2 with its well-characterized partner, the MTR4 helicase (MTREX), as well as with multiple splicing factors. Notably, we also identified interactions with chromatin-associated proteins involved in transcription, including the Polymerase-Associated Factor 1 (PAF1) complex and elongating forms of RNA polymerase II (RNAPII). To further investigate NRDE2 function, we conducted RNA-seq following its transient depletion. Differential expression analysis revealed that loss of NRDE2 alters the expression of thousands of genes. Consistent with earlier reports, we observed splicing defects, particularly intron retention; however, our results indicate that the impact of NRDE2 on intron retention is more extensive than previously recognized. Moreover, intron retention was frequently associated with reduced mRNA expression. Together, these findings suggest that NRDE2 associates with both transcriptional and splicing machineries and plays a broader role in RNA processing than previously appreciated.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300403","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 Transferrin Receptor 1 for Enhancing Drug Delivery Through the Blood-Brain Barrier for Alzheimer's Disease.","authors":"Xinai Shen, Huan Li, Beiyu Zhang, Yunan Li, Zheying Zhu","doi":"10.3390/ijms26199793","DOIUrl":"10.3390/ijms26199793","url":null,"abstract":"<p><p>Drug delivery to the brain faces a critical obstacle in the form of the blood-brain barrier (BBB), which severely limits therapeutic options for Alzheimer's disease (AD). Transferrin receptor 1 (TfR1) is abundantly expressed in brain capillary endothelial cells, offering a potential pathway for circumventing this barrier. Physiologically, TfR1 binds to iron-laden transferrin, leading to cellular uptake through clathrin-mediated endocytosis. Within acidic endosomes, the iron is released, and the receptor-apotransferrin complex recycles to the cell surface for further rounds of transport. Furthermore, studies in AD mouse models have demonstrated that TfR1 expression in brain microvessels remains stable, highlighting its suitability as a delivery target even in disease conditions. Based on this, various drug delivery strategies targeting TfR1 have been developed, including bispecific antibodies, antibody fragments, ligand conjugates, and nanoparticle-based carriers. While these approaches hold great promise, they face practical limitations such as competition with endogenous transferrin, receptor saturation, and inefficient intracellular trafficking. This review details the current understanding of TfR1-mediated BBB transport mechanisms, evaluates emerging delivery platforms, and argues that TfR1 represents an accessible gateway for brain-targeted therapeutics in AD. The insights presented will be of interest to researchers in molecular biology, pharmacology, and drug development.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300554","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":"<i>OsPIP2;1</i> Positively Regulates Rice Tolerance to Water Stress Under Coupling of Partial Root-Zone Drying and Nitrogen Forms.","authors":"Chunyi Kuang, Ziying Han, Xiang Zhang, Xiaoyuan Chen, Zhihong Gao, Yongyong Zhu","doi":"10.3390/ijms26199782","DOIUrl":"10.3390/ijms26199782","url":null,"abstract":"<p><p>The coupling of partial root-zone drying (PRD) with nitrogen forms exerts an interactive \"water-promoted fertilization\" effect, which enhances rice (<i>Oryza sativa</i> L.) growth and development, improves water use efficiency (WUE), mediates the expression of aquaporins (AQPs), and alters root water conductivity. In this study, gene cloning and CRISPR-Cas9 technologies were employed to construct overexpression and knockout vectors of the <i>OsPIP2;1</i> gene, which were then transformed into rice (cv. Meixiangzhan 2). Three water treatments were set: normal irrigation (CK); partial root-zone drying (PRD); and 10% PEG-simulated water stress (PEG), combined with a nitrogen form ratio of ammonium nitrogen (NH₄⁺) to nitrate nitrogen (NO₃^-) at 50:50 (A50/N50) for the coupled treatment of rice seedlings. The results showed that under the coupled treatment of PRD and the aforementioned nitrogen form, the expression level of the <i>OsPIP2;1</i> gene in roots was upregulated by 0.62-fold on the seventh day, while its expression level in leaves was downregulated by 1.84-fold. Overexpression of <i>OsPIP2;1</i> enabled Meixiangzhan 2 to maintain a higher abscisic acid (ABA) level under different water conditions, which helped rice reduce water potential and enhance water absorption. Compared with the CK treatment, overexpression of <i>OsPIP2;1</i> increased the superoxide dismutase (SOD) activity of rice under PRD by 26.98%, effectively alleviating tissue damage caused by excessive accumulation of O₂^-. The physiological and biochemical characteristics of <i>OsPIP2;1</i>-overexpressing rice showed correlations under PRD and A50/N50 nitrogen form conditions, with WUE exhibiting a significant positive correlation with transpiration rate, chlorophyll content, nitrogen content, and Rubisco enzyme activity. Overexpression of <i>OsPIP2;1</i> could promote root growth and increase the total biomass of rice plants. The application of the <i>OsPIP2;1</i> gene in rice genetic engineering modification holds great potential for improving important agricultural traits of crops. This study provides new insights into the mechanism by which the AQP family regulates water use in rice and has certain significance for exploring the role of AQP genes in rice growth and development as well as in response to water stress.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145299840","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":"Challenges in Applying DNA-Binding Protein Predictors to Biological Research.","authors":"Graydon Cowgill, Steven Anthony Strazza, Savannah Wilson, Ranjeeta Odari, Sadia Afrin Bristy, Yongjian Qiu, Sayaka Miura","doi":"10.3390/ijms26199785","DOIUrl":"10.3390/ijms26199785","url":null,"abstract":"<p><p>DNA binding proteins play a crucial role in regulating gene expression, DNA replication, and chromatin organization. While many DNA-binding proteins have been identified, many unique DNA-binding proteins in non-model organisms and recently evolved lineage- or species-specific proteins remain uncharacterized or often lack experimental validation. In addition, genetic variants may alter previously known DNA-binding proteins, leading to loss of binding ability. To address this gap, various computational tools have been developed to predict DNA-binding proteins from protein sequences or structures. Yet, their real-world utility in biological research remains uncertain. To evaluate their effectiveness, we assessed the availability and predictive performance of existing tools using five real-world case studies. We found that most tools were web-based, offering accessibility to researchers without computational expertise. However, many suffered from poor maintenance, including frequent server connection problems, input errors, and long processing times. Among the ten tools that were functional and practical, we found that prediction scores often failed to reflect incorrect outputs, and multiple methods frequently produced the same erroneous predictions. Overall, even a small number of misclassifications can significantly distort biological interpretation, indicating that current DNA-binding prediction tools are not yet sufficiently reliable for empirical research.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145300199","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}