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RETRACTED: Richards et al. Protein Tyrosine Phosphatase Non-Receptor 11 (PTPN11/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC). Int. J. Mol. Sci. 2023, 24, 10545. 撤稿:Richards等人。蛋白酪氨酸磷酸酶非受体11 (PTPN11/Shp2)作为非小细胞肺癌(NSCLC)的驱动癌基因和新的治疗靶点Int。[j] .生物医学工程学报,2016,33(2):444 - 444。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-29 DOI: 10.3390/ijms27093976
Cathy E Richards, Yasir Y Elamin, Aoife Carr, Kathy Gately, Shereen Rafee, Mattia Cremona, Emer Hanrahan, Robert Smyth, Daniel Ryan, Ross K Morgan, Susan Kennedy, Lance Hudson, Joanna Fay, Kenneth O'Byrne, Bryan T Hennessy, Sinead Toomey
{"title":"RETRACTED: Richards et al. Protein Tyrosine Phosphatase Non-Receptor 11 (<i>PTPN11</i>/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC). <i>Int. J. Mol. Sci.</i> 2023, <i>24</i>, 10545.","authors":"Cathy E Richards, Yasir Y Elamin, Aoife Carr, Kathy Gately, Shereen Rafee, Mattia Cremona, Emer Hanrahan, Robert Smyth, Daniel Ryan, Ross K Morgan, Susan Kennedy, Lance Hudson, Joanna Fay, Kenneth O'Byrne, Bryan T Hennessy, Sinead Toomey","doi":"10.3390/ijms27093976","DOIUrl":"https://doi.org/10.3390/ijms27093976","url":null,"abstract":"<p><p><i>IJMS</i> is retracting the article titled \"Protein Tyrosine Phosphatase Non-Receptor 11 (<i>PTPN11</i>/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC)\" [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13131995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814315","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
Electrophysiological and Molecular Features of Remdesivir-Induced Cardiac Toxicity in Male and Female Guinea Pigs. 雷德西韦致雄性和雌性豚鼠心脏毒性的电生理和分子特征。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083685
Chen Zhu, Kun Fu, Hu Wen, Guangqi Chen, Henggui Zhang
{"title":"Electrophysiological and Molecular Features of Remdesivir-Induced Cardiac Toxicity in Male and Female Guinea Pigs.","authors":"Chen Zhu, Kun Fu, Hu Wen, Guangqi Chen, Henggui Zhang","doi":"10.3390/ijms27083685","DOIUrl":"10.3390/ijms27083685","url":null,"abstract":"<p><p>The global spread of COVID-19 led to the rapid authorization of remdesivir as the first antiviral therapy. However, accumulating clinical evidence has linked its use to cardiac adverse effects. Understanding the mechanisms underlying remdesivir-induced cardiotoxicity is critical for optimizing its clinical use and ensuring patient safety. This study investigates the electrophysiological and molecular features underlying remdesivir-induced cardiac toxicity in male and female guinea pigs, aiming to elucidate the sex-dependent differences in cardiac dysfunction and the role of mitochondria in mediating these effects. A cardiac injury model was established via intraperitoneal administration of remdesivir. In vivo telemetry and ex vivo electrocardiography were used for continuous monitoring of cardiac electrical activity, while optical mapping enabled the assessment of action potential parameters and conduction properties. The histopathological alterations and mitochondrial ultrastructure were examined by hematoxylin-eosin staining and transmission electron microscopy. ELISA and Western blot analyses were performed to explore the inflammatory signaling, apoptosis, and mitochondrial dynamics. Remdesivir induced distinct sex-specific patterns of cardiac toxicity. Compared with female guinea pigs, male guinea pigs had significantly more severe myocardial injury, which was characterized by extensive inflammatory cell infiltration, marked mitochondrial disruption, and a higher incidence of sustained ventricular tachyarrhythmia. Overall, remdesivir was associated with sex-dependent cardiac toxicity, accompanied by mitochondrial impairment and inflammatory activation. Male guinea pigs were more susceptible to electrophysiological instability and mitochondrial dysfunction. These findings highlight the importance of carefully evaluating remdesivir's cardiac effects and support the need for individualized, sex-specific considerations in its clinical administration.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814709","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
Machine Learning-Driven QSRR Modeling of Albumin Binding in Fluoroquinolones: An SVR Approach Supported by HSA Chromatography. 机器学习驱动的氟喹诺酮类药物白蛋白结合的QSRR建模:HSA色谱支持的SVR方法。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083700
Yash Raj Singh, Wiktor Nisterenko, Joanna Fedorowicz, Jarosław Sączewski, Daniel Szulczyk, Katarzyna Ewa Greber, Wiesław Sawicki, Krzesimir Ciura
{"title":"Machine Learning-Driven QSRR Modeling of Albumin Binding in Fluoroquinolones: An SVR Approach Supported by HSA Chromatography.","authors":"Yash Raj Singh, Wiktor Nisterenko, Joanna Fedorowicz, Jarosław Sączewski, Daniel Szulczyk, Katarzyna Ewa Greber, Wiesław Sawicki, Krzesimir Ciura","doi":"10.3390/ijms27083700","DOIUrl":"10.3390/ijms27083700","url":null,"abstract":"<p><p>Human serum albumin (HSA) binding critically influences drug distribution and pharmacokinetics. In this study, HSA affinity chromatography was integrated with machine-learning-based quantitative structure-retention relationship (QSRR) modeling to elucidate structural determinants of albumin binding in a library of 115 fluoroquinolone (FQs) derivatives. Experimentally determined log<i>k</i><sub>HSA</sub> values were obtained using biomimetic chromatography, and these were then used as modelling endpoints. Following descriptor reduction via Least Absolute Shrinkage and Selection Operator (LASSO) and systematic benchmarking of 42 regression algorithms, support vector regression (SVR) and nu-support vector regression (ν-SVR) with radial basis function kernels demonstrated superior predictive performance. A parsimonious 12-descriptor ν-SVR model achieved strong calibration and validation metrics (R<sup>2</sup> = 0.916, Q<sup>2</sup><sub>test</sub> = 0.823, concordance correlation coefficient (CCC) = 0.899) and satisfied Organisation for Economic Co-operation and Development (OECD) criteria, including applicability domain assessment. Shapley Additive exPlanations (SHAP)-based interpretation revealed that albumin binding is governed by a balance between hydrophobic surface area and distributed electronic properties, whereas excessive localized polarity and quaternary ammonium functionalities reduce affinity. This experimentally anchored and interpretable modeling framework provides mechanistic insight into HSA binding in fluoroquinolones and offers a robust tool for rational pharmacokinetic optimization. Furthermore, in order to make the model easily accessible to users, we have packaged it in the form of an online application.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814976","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
Hexavalent Chromium Toxicity in the Pancreas: A Study on the Protective Effects of Hypericum perforatum Extract. 六价铬对胰腺的毒性:贯叶连翘提取物的保护作用研究。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083706
Jelena Savici, Simona Marc, Oana-Maria Boldura, Catalin Cicerone Grigorescu, Cristina Paul, Cristina Văduva, Diana Brezovan
{"title":"Hexavalent Chromium Toxicity in the Pancreas: A Study on the Protective Effects of <i>Hypericum perforatum</i> Extract.","authors":"Jelena Savici, Simona Marc, Oana-Maria Boldura, Catalin Cicerone Grigorescu, Cristina Paul, Cristina Văduva, Diana Brezovan","doi":"10.3390/ijms27083706","DOIUrl":"10.3390/ijms27083706","url":null,"abstract":"<p><p>Hexavalent chromium, a widespread heavy metal, induces apoptosis via the mitochondrial pathway through <i>Bax</i> (pro-apoptotic) and <i>Bcl2</i> (anti-apoptotic) proteins. <i>Hypericum perforatum</i>, rich in antioxidants, can neutralise free radicals. This study investigated the effects of CrVI on the pancreas and the protective role of <i>Hypericum perforatum</i>. Five groups of animals were used: control, Cr (CrVI for 3 months), CrH (CrVI + 2.5% <i>Hypericum perforatum</i> extract made from flowers, for 3 months), Cr2 (CrVI for 3 months + distilled water for 1 month), and CrH2 (CrVI for 3 months + <i>Hypericum perforatum</i> extract for 1 month). Samples were collected for histological analysis, gene expression (qRT-PCR), and blood glucose level analysis. CrVI exposure (Cr, Cr2) caused pancreatic damage: oedema, reduced islet size, endocrine cell vacuolisation, and endothelial swelling. Lesions were milder in CrH, while CrH2 resembled the control group. The <i>Bax/Bcl2</i> ratio increased under CrVI (highest in Cr2), indicating apoptosis, but decreased toward control values in CrH and CrH2. Blood glucose levels confirmed these findings. CrVI proved toxic to the endocrine pancreas, inducing structural and molecular alterations that impaired carbohydrate metabolism. Administration of <i>Hypericum perforatum</i> extract reduced these effects, confirming its antioxidant action and potential as a protective agent against CrVI-induced oxidative stress.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815008","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
Phylogenomic Insights into High Conservation and Lineage-Specific Expansion of the ABAPT Gene Family in Plants. ABAPT基因家族在植物中的高度保守性和谱系特异性扩增的系统基因组研究。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083691
Huan Song, Weiwei Li, Hong Xue, Mingming Zhang, Weiwei Zhang, Aoyu Chen, Lei Wang, Quanzhong Dong, Meng Zhang
{"title":"Phylogenomic Insights into High Conservation and Lineage-Specific Expansion of the ABAPT Gene Family in Plants.","authors":"Huan Song, Weiwei Li, Hong Xue, Mingming Zhang, Weiwei Zhang, Aoyu Chen, Lei Wang, Quanzhong Dong, Meng Zhang","doi":"10.3390/ijms27083691","DOIUrl":"10.3390/ijms27083691","url":null,"abstract":"<p><p>De-S-acylation enzymes mediate the reversible S-acylation cycle and play critical roles in plant development and stress responses. However, the precise origin and evolutionary dynamics of this gene family in plants remain poorly understood. In this study, a total of 718 <i>ABAPT</i> genes were identified across 73 plant genomes, including 622 <i>ABHD17</i> and 96 <i>ABHD13</i> homologs, which share only a 20-30% conserved sequence identity between them. We further performed comprehensive analyses of gene duplication and structure, protein properties, synteny networks, and expression profiles to establish a systematic framework by classifying <i>ABAPT</i> genes in land plants. Our results revealed that <i>ABHD13</i> genes have been retained as a single copy in most angiosperm genomes, whereas <i>ABHD17</i> genes have undergone extensive expansion. <i>ABAPT</i> genes formed three major evolutionary clades: Clade 1 contained <i>ABHD13</i> homologs, while Clades 2 and 3 harbored <i>ABHD17</i> homologs. The three clades showed distinct disparities in intron-exon structural patterns and IDR properties. Phylogenomic synteny network analyses revealed the deeply conserved genomic syntenies within each of the six <i>ABAPT</i> subclades among the three clades, while Cluster4-Monocot was more dynamic and showed distinct lineage-specific duplication patterns restricted to Poaceae. <i>ABHD13s</i> exhibited constitutive expression patterns, while the tissue-specific expression genes were predominantly found within the <i>ABHD17s</i> subfamily. Notably, the <i>ABAPT8/9</i> subgroups were specifically expressed in reproductive organs, and the weighted gene co-expression network identified specific groups to find <i>ABAPT</i>-specific regulatory features, implying the presence of potential modules for the protein S-acylation cycle during pollen development. Additionally, our results suggested that C-terminal Cys-rich region was required for ABAPT10 localization. Altogether, this study sheds light on the evolutionary divergence of the <i>ABAPT</i> subclades across major green plant lineages and emphasizes the need for future functional characterizations.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815051","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
Metabolic and Genetic Alterations in Early and Exudative Age-Related Macular Degeneration: Inosine, Amino Acids, and COL2A1 Gene Variant. 早期和渗出性年龄相关性黄斑变性的代谢和遗传改变:肌苷、氨基酸和COL2A1基因变异。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083697
Akvile Bruzaite, Alvita Vilkeviciute-Petraite, Dzastina Cebatoriene, Dalia Zaliuniene, Ieva Ciapiene, Alina Smalinskiene, Loresa Kriauciuniene, Rasa Liutkeviciene
{"title":"Metabolic and Genetic Alterations in Early and Exudative Age-Related Macular Degeneration: Inosine, Amino Acids, and <i>COL2A1</i> Gene Variant.","authors":"Akvile Bruzaite, Alvita Vilkeviciute-Petraite, Dzastina Cebatoriene, Dalia Zaliuniene, Ieva Ciapiene, Alina Smalinskiene, Loresa Kriauciuniene, Rasa Liutkeviciene","doi":"10.3390/ijms27083697","DOIUrl":"10.3390/ijms27083697","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a complex retinal disease influenced by genetic and metabolic factors. Genetic variants impact disease susceptibility, while alterations in amino acid and purine metabolism are involved in AMD development. This study aimed to examine the association between the <i>COL2A1</i> rs1635529 polymorphism and AMD, as well as its relation to specific metabolites. The study comprised 919 participants: 261 with early AMD, 229 with exudative AMD, and 429 controls. DNA was extracted using the salting-out method, and genotyping was performed using real-time PCR. Metabolite levels were analysed with liquid chromatography-mass spectrometry. Statistical analysis was conducted using IBM SPSS Statistics 27.0. Logistic regression revealed that carriers of the GT + TT genotypes had a 1.63-fold higher risk of early AMD (<i>p</i> = 0.046). The T allele was also linked to a 1.67-fold elevated risk (<i>p</i> = 0.033). No significant associations were observed in exudative AMD. Furthermore, lower leucine levels were noted in exudative AMD patients, and inosine levels were reduced in GT genotype carriers within the early AMD group. The <i>COL2A1</i> rs1635529 polymorphism showed a nominal association with early AMD, but not exudative AMD. Differences in leucine and inosine levels were observed, suggesting a potential link between genetic variation and metabolic alterations. These findings indicate possible involvement of collagen-related and metabolic pathways in early disease development; however, the results should be interpreted with caution and require validation in larger studies.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815060","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
Establishment and Characterization of a Stable hERG Cell Line for High-Throughput Drug Cardiac Safety Screening. 用于高通量药物心脏安全性筛选的稳定hERG细胞系的建立和表征。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083701
Hailin Lu, Qingqing Guo, Qinling Qiu, Jiying Hu
{"title":"Establishment and Characterization of a Stable hERG Cell Line for High-Throughput Drug Cardiac Safety Screening.","authors":"Hailin Lu, Qingqing Guo, Qinling Qiu, Jiying Hu","doi":"10.3390/ijms27083701","DOIUrl":"10.3390/ijms27083701","url":null,"abstract":"<p><p>The hERG potassium channel is critical for cardiac ventricular repolarization and a core target in pre-clinical drug safety screening. A robust, stable cell line with uniform, high hERG expression is essential for high-throughput assessments. In this study, we established a functional stable HEK293T cell line with high hERG expression. The hERG gene was subcloned into Lenti-HA-hERG-P2A-EGFP plasmid, in which GFP serves as a selection marker via a P2A self-cleaving peptide. GFP-positive monoclonal cells were isolated by fluorescence-activated cell sorting (FACS). Confocal imaging confirmed that hERG localized predominantly to the cell membrane, consistent with its physiological role. Manual patch-clamp revealed canonical hERG current properties: a small, stable current during depolarization to 20 mV, followed by a large outward tail current upon repolarization to -40 mV-a hallmark of hERG channel gating. Automated patch-clamp (APC)-based current profiling showed 93.5% of stable hERG cells exhibited peak tail currents > 50 pA (87% > 100 pA, with 49.5% > 400 pA), whereas 100% of blank HEK293T cells showed peak tail currents < 50 pA. Pharmacological validation with E-4031 demonstrated concentration-dependent inhibition of hERG currents, with an IC<sub>50</sub> of 29.8 nM, which is consistent with literature-reported values. The stable hERG-expressing HEK293T cell line developed here exhibits consistent hERG expression, canonical channel function, and physiological sensitivity to hERG blockers. When paired with high-throughput APC systems, this cell model provides a robust, standardized platform for pre-clinical drug-induced hERG inhibition evaluation, aiding early detection of long QT syndrome risks and safer drug development.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814756","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
Dual Pathways of UBE4B Inhibit Apoptosis in p53-Positive Tumor Cells via CCAR2 Degradation. UBE4B双通路通过CCAR2降解抑制p53阳性肿瘤细胞凋亡
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083682
Bo Jin, Junyao Qu, Peng Xu, Bo Zhao, Xianting Jiao
{"title":"Dual Pathways of UBE4B Inhibit Apoptosis in p53-Positive Tumor Cells via CCAR2 Degradation.","authors":"Bo Jin, Junyao Qu, Peng Xu, Bo Zhao, Xianting Jiao","doi":"10.3390/ijms27083682","DOIUrl":"10.3390/ijms27083682","url":null,"abstract":"<p><p>Apoptosis, or programmed cell death, is a fundamental process essential for tissue homeostasis, development, and the elimination of damaged or potentially cancerous cells. Here, we identify the E3/E4 ubiquitin ligase UBE4B as a critical suppressor of apoptosis in p53-proficient tumor cells, functioning through a previously uncharacterized dual mechanism. Initially, an orthogonal ubiquitin transfer screening approach identified CCAR2 as a UBE4B substrate. We demonstrate that UBE4B interacts with and ubiquitinates CCAR2, promoting its proteasomal degradation. Furthermore, we found that UBE4B concurrently targets p53 itself for ubiquitin-dependent degradation. Functionally, UBE4B overexpression suppresses apoptosis, whereas rescue experiments indicate that restoring p53 expression reverses this suppression more effectively than restoring CCAR2, highlighting the dominance of the direct p53 degradation pathway. Mechanistically, UBE4B deficiency leads to CCAR2 accumulation, which inhibits SIRT1 activity, thereby enhancing p53 acetylation and stability; this effect is reversed upon CCAR2 co-depletion. Consistently, transcriptional profiling confirms that UBE4B downregulates key p53 target genes (e.g., BAX, PUMA) through this dual-pathway regulation. In summary, our study establishes that UBE4B acts as a key apoptosis suppressor by coordinately degrading both p53 and its positive regulator CCAR2, revealing a targetable vulnerability in p53-wild-type tumors.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815053","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 Preliminary Study for the Trial of Using Selected miRNAs for the Laboratory Diagnosis of Colorectal Cancer. 筛选mirna用于结直肠癌实验室诊断试验的初步研究。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083702
Michal Sulikowski, Tadeusz Sulikowski, Mateusz Kurzawski, Damian Malinowski, Elżbieta Urasińska, Monika Rac
{"title":"The Preliminary Study for the Trial of Using Selected miRNAs for the Laboratory Diagnosis of Colorectal Cancer.","authors":"Michal Sulikowski, Tadeusz Sulikowski, Mateusz Kurzawski, Damian Malinowski, Elżbieta Urasińska, Monika Rac","doi":"10.3390/ijms27083702","DOIUrl":"10.3390/ijms27083702","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the second most common cancer in Europe. There is a need to explore and validate new blood-based tumor markers to improve the selection of patients who are likely to benefit from an early, non-invasive diagnosis of CRC. The purpose of this report is to present the test protocol and its verification. The study is planned in four phases. The first trial phase involves collecting material, consisting of healthy tissue, diseased tissue, and plasma, from 120 CRC patients over 50 years old during surgery. This phase also involves identifying microRNAs (miRNAs) and comparing their expressed levels in colorectal cancer cells with those in healthy tissue taken from a standard resection margin. We detected measurable levels of miRNAs in tissue samples taken from patients, confirming that the material was correctly removed for testing. Statistically significant differences were obtained between healthy and cancerous tissue for selected miRNAs. Some of the selected miRNAs have higher expression levels in CRC tissue and could be potential candidate biomarkers for laboratory-based colorectal cancer diagnosis.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 8","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814885","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
Liposomal Encapsulation of Camptothecin/Carboxymethyl-β-Cyclodextrin Complexes: Stability, Solubility and Cytotoxicity. 喜树碱/羧甲基β-环糊精配合物的脂质体包封:稳定性、溶解度和细胞毒性。
IF 4.9 2区 生物学
International Journal of Molecular Sciences Pub Date : 2026-04-21 DOI: 10.3390/ijms27083705
Fernando Mesías-Recamán, Alba Durán-Moreno, Thais Carmona, Gema Marcelo, Francisco Mendicuti
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