International Journal of Molecular Sciences最新文献

{"title":"Special Issue \"Zebrafish: A Model Organism for Human Health and Disease: 2nd Edition\".","authors":"Jyotshna Kanungo","doi":"10.3390/ijms27209296","DOIUrl":"10.3390/ijms27209296","url":null,"abstract":"<p><p>The era of using zebrafish (<i>Danio rerio</i>) as a model to investigate human disease began in the 1960s with the pioneering work by a molecular biologist, George Streisinger, who established its role as a genetic vertebrate model [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267377","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":"Non-Canonical HIF2 Accumulation in Breast Cancer Cells.","authors":"Karolina Kozal, Aleksandra Opitz, Monika Jarosiewicz, Michał Juszczak, Anna Krześlak","doi":"10.3390/ijms27209306","DOIUrl":"10.3390/ijms27209306","url":null,"abstract":"<p><p>Metabolic reprogramming drives cancer aggressiveness. While hypoxia-inducible factor 1 (HIF1) is commonly associated with glycolysis regulation, the under-investigated HIF2 isoform may also modulate the metabolic profile of breast cancer. We investigated the role of non-canonical HIF2 activation in metabolic adaptation to nutrient availability by culturing MDA-MB-231 and MCF-7 cells under normoxia with varying glucose and glutamine concentrations. Using RNA interference, we downregulated HIF2 and analyzed HIF isoforms and metabolic targets (GLUT1, HK2, PKM2, PDK1) at the transcriptional and protein levels. We observed a new, non-canonical accumulation of HIF2 in MDA-MB-231 cells associated with glucose and glutamine restriction, a phenomenon absent in MCF-7 cells. In MDA-MB-231 cells, silencing <i>HIF2A</i> under standard conditions significantly decreased PDK1 mRNA expression. At the protein level, HIF2 downregulation altered metabolic targets in a context-dependent manner under nutrient restriction. Adding a hypoxia-mimetic (CoCl₂) did not fully restore the protein expression patterns, suggesting that HIF2 accumulation may contribute to these context-dependent shifts. HIF2 downregulation decreased glycolytic efficiency under low-glucose conditions. Our findings suggest that HIF2 might modulate the metabolic plasticity of MDA-MB-231 cells through distinct changes in gene expression and post-translational mechanisms. This provides support for investigating the HIF2 isoform while studying breast cancer metabolism and considering it as a potential target for treating triple-negative breast cancer.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267219","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":"Antitumor Effects of Melittin-Functionalized Fe₃O₄ Magnetic Nanoparticles in Collagen-I-Based Caco-2/BJ/HUVEC Spheroids Enhanced by Magnetic Hyperthermia.","authors":"Alex Câmpian, Ioana Bâldea, Mara Muntean, Cristian Iacoviță, Nicoleta Decea, Adrian Florea","doi":"10.3390/ijms27209302","DOIUrl":"10.3390/ijms27209302","url":null,"abstract":"<p><p>This study evaluated the integrated biochemical and ultrastructural response of three-dimensional colorectal cancer spheroids to magnetic hyperthermia (MH) mediated by melittin-functionalized Fe₃O₄ magnetic nanoparticles (MNPs-Mel). The spheroids comprised human Caco-2 colorectal adenocarcinoma cells, dermal fibroblasts (BJ), and human umbilical vein endothelial cells (HUVECs) in a ratio of 3:1:1 in a collagen-I matrix. They were assigned to control, alternating magnetic field (AMF) control (Control-MH), free melittin (Mel), unloaded MNPs, MNPs-MH, MNPs-Mel, and MNPs-Mel-MH groups and assessed at 24 and 72 h. MTS-reducing activity (colorimetry) and ATP-associated luminescence were quantified as viability markers, while VEGF, HIF-1α, and caspase-9 concentrations measured by ELISA were used to assess angiogenesis and apoptosis induction. MNPs' size, shape and internalization and treatment-associated ultrastructural changes were examined by transmission electron microscopy (TEM). Treatment, time, and their interaction significantly affected all biochemical endpoints. Every intervention reduced MTS absorbance relative to control at both time points. MNPs-Mel produced lower MTS values than unloaded MNPs, whereas MNPs-Mel-MH generated the lowest ATP signal at both time points and the lowest MTS signal at 72 h. The combined treatment also reduced VEGF and increased caspase-9, maximal at 72 h, while the increase in HIF-1α at 24 h was not maintained at 72 h. TEM showed intracellular MNPs-Mel and a more restricted distribution within spheroids than in the separately examined monocultures. Free Mel and unloaded MNPs produced time-dependent ultrastructural changes, while MH accentuated the changes associated with MNP exposure. MNPs-Mel-MH led to pronounced mitochondrial polymorphism, cristae loss, matrix rarefaction, autophagic-lysosomal alterations, endoplasmic reticulum expansion, reduced intercellular adherence, and extensive disruption of Caco-2 cells, particularly at 72 h. However, biochemical endpoints represent the response of the whole spheroid and do not distinguish effects on Caco-2 cells from those on BJ fibroblasts or HUVECs. The molecular and ultrastructural findings identify MNPs-Mel-MH as the treatment associated with the broadest response in this tri-cellular spheroid model, linking sustained metabolic suppression and reduced pro-angiogenic signaling with marked mitochondrial and cellular injury.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266944","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":"Correction: Perkowski et al. Regeneration of Peripheral Blood T-Cell Subpopulations in Children After Completion of Acute Lymphoblastic Leukemia Treatment. <i>Int. J. Mol. Sci.</i> 2025, <i>26</i>, 11107.","authors":"Bartosz Perkowski, Łukasz Słota, Aleksandra Lasia, Tomasz Szczepański, Łukasz Sędek","doi":"10.3390/ijms27209317","DOIUrl":"10.3390/ijms27209317","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13704979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267140","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":"Unveiling Telocyte Networks in the Human Superficial Fascia: A New Component of the Hypodermal Interstitial Microenvironment.","authors":"Mirko Manetti, Lucia Petrelli, Alessia Tani, Cesare Tiengo, Irene Rosa, Carla Stecco","doi":"10.3390/ijms27209331","DOIUrl":"10.3390/ijms27209331","url":null,"abstract":"<p><p>The human superficial fascia (SF) is a dynamic layer within the hypodermis, increasingly recognized for its role in tissue repair, lymphatic drainage, and fascial dysfunctions. Yet the complete cellular landscape of SF remains largely uncharacterized. Telocytes (TCs) are specialized interstitial cells defined by long, moniliform telopodes, serving as \"connecting cells\" in various organs. This study provides the first identification of TCs in human SF using immunohistochemistry, confocal immunofluorescence, and transmission electron microscopy (TEM). CD34+ TCs were widespread across both adipose-rich and fibrous compartments of human SF. Confocal microscopy identified extensive three-dimensional networks of CD34+/PDGFRα+/LGR5+/CD31-/α-SMA-/c-kit- TCs, closely associated with CD34+/CD31+ microvessels and TH+ autonomic nerve fibers. Notably, TCs established strategic spatial relationships with D2-40+ lymphatics and c-kit+ mast cells, raising the possibility of a TC-mast cell functional tandem in interstitial fluid homeostasis. Furthermore, the expression of the stemness marker LGR5 positions TCs as an integral component of perivascular stem cell niches. TEM confirmed the presence of TCs ultrastructurally distinguished by characteristic telopodes. In conclusion, our findings suggest that TCs may act as important regulators of SF integrity and homeostasis. Their identification provides novel insights into fascial anatomy while uncovering potential therapeutic targets for conditions such as lymphedema and impaired wound healing.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267498","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":"Expression of Concern: Son et al. Inhibition of Colony-Stimulating Factor 1 Receptor by PLX3397 Prevents Amyloid Beta Pathology and Rescues Dopaminergic Signaling in Aging 5xFAD Mice. <i>Int. J. Mol. Sci.</i> 2020, <i>21</i>, 5553.","authors":"International Journal Of Molecular Sciences Editorial Office","doi":"10.3390/ijms27209304","DOIUrl":"10.3390/ijms27209304","url":null,"abstract":"<p><p>With this notice, the IJMS Editorial Office alerts readers to concerns regarding this article [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13704939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267175","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":"Genome-Wide Identification and Analysis of the Perennial Ryegrass (<i>Lolium perenne</i> L.) WRKY Family Associated with Heat Stress.","authors":"Wei Chen, Nan Song, Jing Zhang, Bin Xu, Yingjun Chi","doi":"10.3390/ijms27209332","DOIUrl":"10.3390/ijms27209332","url":null,"abstract":"<p><p>Perennial ryegrass, the most widely cultivated forage and turfgrass, exhibits a relatively poor temperature tolerance, which restricts its distribution and utilization in warmer regions. WRKY transcription factors regulate diverse biological processes in plants, including development and stress responses. Here, we report the comprehensive identification of 97 <i>WRKY</i> genes (<i>LpWRKYs</i>) in perennial ryegrass. The <i>LpWRKYs</i> were unevenly distributed across seven chromosomes, with one gene anchored to a scaffold. These genes were classified into three major groups and five subgroups based on phylogenetic relationships and structural domain diversity. All LpWRKYs contained either one or two WRKY domains and the LpWRKYs within the same group had similar motif compositions. A total of 12 tandem duplicates and 27 segmental duplicates were identified, suggesting that gene duplication might have contributed to the expansion of the <i>LpWRKY</i> gene family. Ka/Ks analysis revealed that all duplicated <i>LpWRKY</i> gene pairs were subjected to purifying selection during the evolution. Co-linearity analysis showed strong co-linearity between <i>LpWRKYs</i> and <i>OsWRKYs</i> from rice. <i>Cis</i>-acting elements in the <i>LpWRKY</i> promoters were related to growth and development, phytohormone responses, and stress responses. RNA-seq and qRT-PCR analysis revealed that the expression levels of <i>LpWRKY5/16/33/35</i> were significantly up-regulated, while <i>LpWRKY21</i>/<i>92</i> were significantly down-regulated in roots under heat stress. Additionally, <i>LpWRKY12/21/33/35/43/89/92/96</i> displayed significant down-regulation in leaves under heat stress. It was suggested that these <i>LpWRKYs</i> were potentially associated with the heat-stress response in perennial ryegrass. Notably, <i>LpWRKY33</i> and <i>LpWRKY35</i> exhibited distinct tissue-specific transcriptional patterns in response to heat stress, implying their participation in complex tissue-dependent regulatory networks. Protein interaction prediction further suggested that LpWRKY96 may function as a potential central regulator in the heat response signaling network. Taken together, this study provides clues into the regulatory roles of the WRKY gene family in perennial ryegrass.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13704931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267158","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":"RETRACTED: Abou-ElNaga et al. Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells After Xenograft into Nude Mice. <i>Int. J. Mol. Sci.</i> 2017, <i>18</i>, 813.","authors":"Amoura Abou-ElNaga, Ghada Mutawa, Ibrahim M El-Sherbiny, Hassan Abd-ElGhaffar, Ahmed A Allam, Jamaan Ajarem, Shaker A Mousa","doi":"10.3390/ijms27209309","DOIUrl":"https://doi.org/10.3390/ijms27209309","url":null,"abstract":"<p><p>The journal retracts the article titled \"Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice\" [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244130","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":"Urinary Bisphenol A Levels Are Associated with Vascular Injury in Mexican Patients with Coronary Artery Disease.","authors":"Fernando Manuel Guerrero-Meza, Marco Antonio Alcocer-Gamba, Juan Pablo Núñez-Urquiza, Rafael Vera-Urquiza, Aquiles Montalvo-Ramos, Santiaga Marisela Ahumada-Solórzano, Haydé Azeneth Vergara-Castañeda, Juan Carlos Solís-Sáinz, Ana Gabriela Hernández-Puga","doi":"10.3390/ijms27209295","DOIUrl":"10.3390/ijms27209295","url":null,"abstract":"<p><p>Coronary artery disease (CAD) is a leading cause of death worldwide and is associated with standard modifiable cardiovascular risk factors (SMuRFs); however, additional factors may contribute to its development. Bisphenol A (BPA), an endocrine-disrupting chemical has been associated with cardiovascular alterations. We investigated BPA's possible association with classic risk factors and vascular injury biomarkers in Mexican patients with CAD. Adult patients underwent quantitative coronary angiography and SYNTAX score assessment and were classified as having obstructive (OD) or non-obstructive (NOD) disease. SMuRFs, lipid profile, VCAM-1, MMP-2, MMP-9, and uBPA were determined. Data were analyzed using correlation analysis, Welch's <i>t</i>-test, ANOVA, and adjusted multiple linear regression. Eighty-nine patients aged 30-85 years were evaluated. OD patients had higher uBPA levels (3.46 ± 2.04 ng/mL) than NOD patients (1.25 ± 1.08 ng/mL), and uBPA levels differed according to the number of diseased arteries and diseased artery segments. uBPA was positively associated with MMP-2, MMP-9, SYNTAX score, percentage of stenosis, number of diseased arteries, diseased artery segments, and SMuRFs, and negatively associated with HDLc. SYNTAX score was associated with MMP-2, MMP-9, VCAM-1 and low HDLc levels. Our findings support uBPA levels are associated with vascular injury in Mexican patients with coronary artery disease.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267437","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":"Hypoxic Microenvironment Effects on Matrix Metalloproteinases' Expression and Enzymatic Activity, and HIFs' Expression in Non-Small Cell Lung Cancer Cells.","authors":"Georgina Gonzalez-Avila, Cuauhtemoc Sandoval, Bettina Sommer, A Armando Garcia-Hernandez, Jose S Lopez-Gonzalez, Arnoldo Aquino-Gálvez, Carina Becerril, Edgar Flores-Soto","doi":"10.3390/ijms27209314","DOIUrl":"10.3390/ijms27209314","url":null,"abstract":"<p><p>The hypoxic tumor microenvironment (TME) promotes metastasis, in which matrix metalloproteinases (MMPs) play a central role. The present work aimed to analyze the effects of hypoxia on MMP expression and enzymatic activity, as well as hypoxia-inducible factor (HIF) expression in different non-small cell lung cancer (NSCLC) cells. Cells were cultured in 1% O₂ for 6 and 12 h, and the effects of hypoxia on MMPs and HIFs were analyzed using Western blotting and zymography. The highest MMP-2 protein expression was detected in CALU-1 (<i>p</i> ≤ 0.003) and A549 cells (<i>p</i> ≤ 0.006) at 6 and 12 h, respectively. Higher levels of MMP-9 were detected in CALU-1 (<i>p</i> ≤ 0.003) at 6 h and in A549 cells (<i>p</i> ≤ 0.04) at 12 h. MMP-2 and MMP-9 had the highest enzymatic activity in SKMES-1 cells (<i>p</i> ≤ 0.003). Increased HIF-1α levels were detected in A427 (<i>p</i> ≤ 0.04) at 6 h and in SKLU-1 cells (<i>p</i> ≤ 0.01) at 12 h, while higher HIF-2α expression was found in SKMES-1 at 6 h and 12 h (<i>p</i> ≤ 0.04). In conclusion, although hypoxia induces changes in MMP-2 and MMP-9 expression in NSCLC cells through HIF-dependent or HIF-independent pathways, these effects are not necessarily similar to those observed in enzymatic activity and differ between cell lines.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149267056","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}