IUBMB Life最新文献

{"title":"CircROBO2 Orchestrates Osimertinib Resistance Through miR-625-5p/PDGFB-Mediated MAPK Activation in Non-Small Cell Lung Cancer","authors":"Miao He,&nbsp;Jiang-ying Cai,&nbsp;Ying-ying Wang,&nbsp;Xin Ma,&nbsp;Chong-ge You,&nbsp;Hong-wei Gao","doi":"10.1002/iub.70045","DOIUrl":"https://doi.org/10.1002/iub.70045","url":null,"abstract":"<div>\u0000 \u0000 <p>The emergence of acquired resistance to osimertinib represents a formidable therapeutic challenge in the management of non-small cell lung cancer (NSCLC). While circular RNAs (circRNAs) have been increasingly recognized as crucial modulators of chemotherapeutic resistance, their specific involvement in osimertinib resistance mechanisms remains poorly elucidated. We established osimertinib-resistant NSCLC cell lines (HCC4006OR) through prolonged drug exposure and conducted comprehensive transcriptome sequencing to identify differentially expressed circRNAs. The molecular characteristics and functional implications of circROBO2 were systematically investigated utilizing an array of cellular and molecular biological methodologies. Advanced molecular dynamics simulations were implemented to elucidate the potential molecular interactions between PDGFB and osimertinib. We identified circROBO2 as significantly upregulated in osimertinib-resistant HCC4006OR cells. Functional studies revealed that circROBO2 enhances cell survival, proliferation, and invasion while suppressing apoptosis under osimertinib treatment. Mechanistically, circROBO2 functions as a molecular sponge for miR-625-5p, resulting in elevated PDGFB expression and subsequent activation of the MAPK pathway, particularly the RAF/MEK/ERK cascade. Targeting this pathway through circROBO2 knockdown or miR-625-5p overexpression partially restored osimertinib sensitivity in resistant cells. Molecular dynamics simulations suggested potential direct interactions between PDGFB and osimertinib, providing additional insights into the resistance mechanism. Our study identifies a novel circROBO2/miR-625-5p/PDGFB regulatory axis in osimertinib resistance and positions circROBO2 as a potential therapeutic target and biomarker for NSCLC treatment.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYC-Mediated Osseous Regeneration via BMSCs/PRP/β-TCP/PCL Bioprinted Constructs: Rapid Defect Rehabilitation and Preliminary Clinical Efficacy Evaluation","authors":"Dinghao Luo,&nbsp;Zhaoyang Ran,&nbsp;Junxiang Wu,&nbsp;Lei Wang,&nbsp;Wen Wu,&nbsp;Kai Xie,&nbsp;Liang Deng,&nbsp;Yongqiang Hao","doi":"10.1002/iub.70036","DOIUrl":"https://doi.org/10.1002/iub.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>Bone defects present significant clinical challenges due to their morphological heterogeneity and structural complexity, necessitating regenerative strategies that integrate structural adaptability, biomechanical stability, and osteogenic potential. In this study, a bioengineered construct composed of bone marrow mesenchymal stem cells (BMSCs), platelet-rich plasma (PRP), polycaprolactone (PCL), and β-tricalcium phosphate (β-TCP) was fabricated using 3D bioprinting. In vitro assays assessed osteoprogenitor cell proliferation (CCK-8), migration (Transwell), differentiation (ALP staining), and endothelial tubulogenesis (Matrigel assay). In vivo bone regeneration was evaluated using a rabbit femoral condyle defect model, with histomorphometric analysis (Masson and COL-1 staining). Mechanistic insights were explored via RNA sequencing and western blot analysis. Clinical validation included pre- and postoperative assessments of visual analog scale (VAS) scores and computed tomography (CT) imaging in patients with osseous defects. The bioprinted constructs significantly enhanced BMSCs proliferation (<i>p</i> &lt; 0.01), migration (<i>p</i> &lt; 0.0001), and ALP activity (<i>p</i> &lt; 0.0001), while promoting endothelial tubulogenesis (<i>p</i> &lt; 0.01). In vivo, the BMSCs/PRP/PCL/β-TCP group exhibited greater Masson staining and collagen type I expression than controls at 2 weeks, 1 month, and 6 months postoperatively. Clinically, VAS scores significantly decreased (3.33 ± 1.63 pre-op vs. 0.50 ± 0.84 post-op, <i>p</i> = 0.005) with no severe complications. PRP concentration-dependently upregulated MYC expression (mRNA: <i>p</i> &lt; 0.0001; protein: <i>p</i> &lt; 0.0001), while MYC knockdown abrogated PRP-induced ALP and RUNX2 expression, confirming MYC's regulatory role in osteogenesis. In conclusion, BMSCs/PRP/PCL/β-TCP bioprinted constructs enhance MYC-mediated bone regeneration, demonstrating promising clinical potential for bone defect repair.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The IUBMB Focused Meeting on Aminoacyl-tRNA Synthetases 2023","authors":"Patrick O'Donoghue,&nbsp;Ilka U. Heinemann","doi":"10.1002/iub.70041","DOIUrl":"https://doi.org/10.1002/iub.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>By ligating amino acids to their cognate transfer RNAs (tRNAs), the aminoacyl-tRNA synthetases (AARSs) establish the genetic code in all living cells. This special issue of <i>IUBMB Life</i> is dedicated to the IUBMB Focused Meeting on AARSs in 2023 and includes 12 original research articles and reviews that demonstrate some of the significant advances in AARS biology that were featured at the meeting. The articles focus on the role of AARS variants in human disease, molecular evolution of AARSs, synthetic biology applications involving AARSs, and the roles of AARSs and tRNAs in regulating protein synthesis. Together these studies reveal an expanded understanding of the function of AARSs in diverse cells and organisms and the application of these discoveries to biotechnology and medicine.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deacetylase Inhibitor Trichostatin A Promotes the Proliferation of Epithelial Cells and Suppresses Glycolytic Activity of Fibroblasts in the Kidney","authors":"Marina I. Buyan,&nbsp;Irina B. Pevzner,&nbsp;Andrey I. Buyan,&nbsp;Ljubava D. Zorova,&nbsp;Dmitry B. Zorov,&nbsp;Nadezda V. Andrianova,&nbsp;Egor Y. Plotnikov","doi":"10.1002/iub.70044","DOIUrl":"https://doi.org/10.1002/iub.70044","url":null,"abstract":"<div>\u0000 \u0000 <p>Undesirable tissue fibroblast activation after injury is still an unresolved problem for many organs, including the kidney. Kidney fibroblasts and tubular epithelial cells demonstrate significant differences in gene expression profiles, including metabolism-related genes. As a result, these cell types exhibit differences in the energy metabolism that could be the basis of targeted therapy for fibrosis. Among other deacetylase inhibition is considered a therapeutic approach that could simultaneously promote tissue regeneration and suppress the development of fibrosis, but their relation to bioenergetics has not been considered before. In this study, we aimed to compare the influence of the HDAC inhibitor trichostatin A (TSA) on renal tubular epithelial cells and kidney fibroblasts. We analyzed resemblance and differences in TSA effects on the proliferative activity of the cells and investigated the molecular mechanisms responsible for these effects; e.g., we focused on the activity of signaling pathways associated with cell viability (Akt/mTOR/p70^S6). We found that TSA increased the proliferation rate of epithelial cells, while it tended to decrease the growth rate of fibroblasts. Furthermore, the amount of phosphorylated forms of kinases Akt and P70^S6 increased in epithelial cells after incubation with TSA, indicating the activation of the Akt/mTOR/p70^S6 signaling pathway, while decreasing its activity in fibroblast cells. Since there are differences in the bioenergetics between fibroblasts and epithelial cells, we investigated the impact of TSA on the glycolytic activity of both cell types. Indeed, we showed that TSA reduced the activity of glycolytic processes in fibroblast cells. The observed changes indicate a positive effect of TSA on regenerative versus fibrotic processes in the kidney by reducing the growth and metabolic activity of fibroblasts and activating the proliferation of epithelial cells.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of Initiated Cell Line Derived From NIH3T3 Fibroblasts","authors":"Myeong-Han Ro,&nbsp;Taehyun Park,&nbsp;SungHee Hwang,&nbsp;Hye-Gyo Kim,&nbsp;Michael Lee,&nbsp;Misu Lee","doi":"10.1002/iub.70039","DOIUrl":"https://doi.org/10.1002/iub.70039","url":null,"abstract":"<div>\u0000 \u0000 <p>Autophagy plays contrasting roles depending on the stage of cellular transformation. However, although advanced tumor cell models are abundant, cell lines at the initiation stage of transformation are very limited. Therefore, the development of initiated cell lines—cells that have acquired early genetic alterations but not yet completed the multistep transformation process —is crucial for the development of anticancer drugs targeting autophagy. In this study, we successfully established a new initiated cell line (Foci #3) from foci formed in the in vitro two-stage cell transformation assay with NIH3T3 fibroblast cells. Foci #3 cells retained typical features of epithelial morphology, similar to its parental untransformed NIH3T3 cells. However, unlike NIH3T3 cells, where many dead cells were found during the long-term culture of 40 days, few dead cells were observed in Foci #3 cells. Particularly, the sensitivity of Foci #3 cells to the autophagy inhibitor CQ was higher than that of NIH3T3 cells and similar to that of Bhas 42 cells, the most commonly used initiated cell line. Moreover, Foci #3 cells maintained a higher level of autophagic flux than NIH3T3 cells throughout the extended culture period, indicating acquisition of the characteristic of dependence on autophagy for survival, which is typical of transformed cells. Importantly, qPCR analysis of epithelial–mesenchymal transition gene expression revealed that the Foci #3 cell line exhibited characteristics of both non-tumorigenic and tumorigenic states. Whole-genome sequencing analysis revealed that among the 17 genes with exon mutations in the Foci #3 cells, four were tumor suppressors and eight were involved in oncogenesis. Additionally, the Foci #3 cell line exhibited the loss of copy number variations in several tumor suppressors. Together, our results suggest that the newly developed Foci #3 cell line may be an efficient tool for elucidating the role of autophagy in the early stages of transformation.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Treatment Strategy for Lung Cancer With HDAC and Wnt/β-Catenin Pathway Inhibitors","authors":"Elif Erturk,&nbsp;Oguzhan Akgun,&nbsp;Yaren Yildiz,&nbsp;Gonca Tuna,&nbsp;Ferda Ari","doi":"10.1002/iub.70037","DOIUrl":"https://doi.org/10.1002/iub.70037","url":null,"abstract":"<p>Lung cancer is a type of cancer with high morbidity and mortality rates worldwide. The overall survival rate of lung cancer patients is low due to a lack of therapeutic options. Recently, the combination of histone deacetylase (HDAC) inhibitors with anti-cancer agents offers a promising therapeutic strategy for cancer treatment. Repurposing these drug combinations is important to evaluate their preventive effect on the epithelial mesenchymal transition (EMT) phenotype, which plays a critical role in tumor progression and metastasis. In this study, the changes that the combination of the HDAC inhibitor Valproic acid (VPA) and Wnt/β-Catenin pathway inhibitor Niclosamide (Niclo) may cause in cytotoxicity, apoptosis, cell cycle, and EMT mechanisms in lung cancer cell lines (A549 and H1299) were examined. According to the results, the combination of VPA + Niclo significantly reduced cell viability in lung cancer cells compared to the use of Niclo alone. ELISA and Western blot analyses revealed that the combination of VPA + Niclo significantly enhanced the total acetylation of Histone H3 compared to the use of VPA alone. It was also found that the combination treatment induced apoptosis by increasing the activity of Caspase 3/7 and Annexin-V and significantly increased the percentage of apoptotic cells by causing depolarization of mitochondria. After cell cycle analysis, the combination treatment increased G1 phase retention in A549 cells, while G1-G2/M phase retention increased in H1299 cells. Wound healing and transwell migration assay results showed that the VPA + Niclo combination treatment inhibited cell migration in lung cancer cells. According to Western blot and PCR results, after VPA + Niclo treatment, the increase in E-Cadherin levels and the decrease in <i>β</i>-Catenin, Fibronectin, Vimentin, and N-Cadherin levels at both protein and gene levels indicated that combination therapy may be useful in preventing the EMT process in lung cancer cells. As a result of the analyses, it was seen that VPA + Niclo combination therapy could play a critical role in preventing the acquisition of the mesenchymal phenotype, reducing cell migration and invasion ability, and preventing tumor cell survival and resistance to apoptosis. In conclusion, it was determined that VPA + Niclo combination treatment shows anticancer activity in lung cancer cells and is a promising approach that may have a synergistic effect in inhibiting EMT.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Underlining the Molecular Mechanism of Nonalcoholic Fatty Liver Disease and Coronary Artery Disease in Lipid Metabolism by Combining Multiple Sets of Data Sets","authors":"Wei Zheng,&nbsp;Shouhao Wang,&nbsp;Huafang Wang,&nbsp;Chengan Xu,&nbsp;Qiaoqiao Yin,&nbsp;Hua Di","doi":"10.1002/iub.70040","DOIUrl":"https://doi.org/10.1002/iub.70040","url":null,"abstract":"<p>Nonalcoholic fatty liver disease (NAFLD) is closely associated with coronary artery disease (CAD); however, their shared genetic traits and molecular mechanisms in lipid metabolism remain unclear. In this study, we identified that the differentially expressed genes in NAFLD and CAD intersected with lipid metabolism genes to obtain three key genes—GPD1, MVK, and PIK3R2. Data from the GeneCards database indicated a significant correlation between NAFLD-related regulatory genes and the expression levels of these key genes. Notably, GPD1 showed a significant positive correlation with PNPLA3 (<i>r</i> = 0.715), while PIK3R2 exhibited a significant negative correlation with MIR21 (<i>r</i> = −0.691). Similarly, CAD regulatory genes were significantly correlated with the expression levels of these key genes; GPD1 showed a significant positive correlation with APOA1 (<i>r</i> = 0.751), and PIK3R2 had a significant negative correlation with LPA (<i>r</i> = −0.362). Additionally, single-cell sequencing analysis of NAFLD showed that GPD1, MVK, and PIK3R2 had higher activity in cells with a high expression of bile acid metabolism genes in the immune pathway. In CAD, GPD1 showed higher activity in cells with high oxidative phosphorylation in the immune pathway. Finally, we found that one drug interacted with MVK, while 38 drugs interacted with PIK3R2. This study highlights GPD1, MVK, and PIK3R2 as key genes involved in NAFLD, CAD, and lipid metabolism, suggesting potential targets for further mechanistic studies and novel therapeutic approaches for patients with NAFLD and CAD.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPP1 Regulates SASP via the p53 Signaling Pathway to Affect ALI Progression","authors":"Congcong Yuan,&nbsp;Shilong Zhao,&nbsp;Wentao Ma,&nbsp;Hongjun Na,&nbsp;Qiuyue Tan,&nbsp;Jing Gao","doi":"10.1002/iub.70038","DOIUrl":"https://doi.org/10.1002/iub.70038","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute lung injury (ALI) is a condition with acute respiratory failure caused by various factors, characterized by severe hypoxemia and diffuse alveolar damage, involving multiple cytokines and signaling pathways. This study investigates the role of secreted phosphoprotein 1 (SPP1) in ALI and explores its underlying mechanisms through a series of in vitro and in vivo experiments. Our results demonstrate that SPP1 expression is significantly upregulated in ALI animal models, correlating with increased oxidative stress and inflammatory responses. In LPS-induced lung injury models, elevated levels of malondialdehyde (MDA) and IL1β, along with decreased superoxide dismutase (SOD) levels, were observed, further confirming the active state of SPP1 in ALI. In vitro experiments using BEAS-2B cells revealed that LPS treatment increased IL1β and reactive oxygen species (ROS) levels while decreasing SOD levels, with concomitant upregulation of SPP1. SPP1 knockdown significantly inhibited these changes, directly confirming its regulatory role in ALI progression. We further explored the regulatory mechanisms of SPP1 on the senescence-associated secretory phenotype (SASP), a key pathological process in ALI. SA-β-GAL staining and γ-H2AX results indicated elevated cellular senescence in LPS-treated cells and ALI models. SPP1 knockdown reduced senescence markers, enhanced cell viability, decreased apoptosis, and improved cell proliferation capacity, suggesting that SPP1 promotes ALI via the SASP phenotype. Mechanistically, we found that SPP1 regulates ALI via the p53 signaling pathway. LPS treatment increased p-p53 levels, whereas SPP1 knockdown reduced p53 activation. The use of a p53 inhibitor further suppressed SASP and improved ALI-related indicators. Animal model validation corroborated these findings, showing that SPP1 knockdown and p53 inhibitor treatment reduced lung tissue damage and improved ALI-related indicators. Collectively, our study reveals a novel mechanism by which SPP1 regulates ALI progression via the p53 signaling pathway and SASP. This discovery not only enriches our understanding of ALI pathogenesis but also provides a new therapeutic target and potential intervention strategies for ALI treatment.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fungi and Myxomycetes of the Tehuacán-Cuicatlán Biosphere Reserve, Mexico: A Comprehensive Review and Future Perspectives","authors":"Julio Mena-Portales,&nbsp;Yordanis Pérez-Llano,&nbsp;Marco Antonio Vásquez-Dávila,&nbsp;Taimy Cantillo,&nbsp;Gladys Isabel Manzanero-Medina,&nbsp;María del Rayo Sánchez-Carbente,&nbsp;Ramón Alberto Batista-García","doi":"10.1002/iub.70034","DOIUrl":"https://doi.org/10.1002/iub.70034","url":null,"abstract":"<p>The Tehuacán-Cuicatlán Biosphere Reserve in Mexico, spanning approximately 10,000 km², is crucial for conserving arid and semi-arid ecosystems, as it hosts unique endemic species and complex ecological interactions. Despite their environmental significance, fungi and myxomycetes in this region have been understudied, particularly those adapted to extreme conditions. These organisms are vital for nutrient cycling, soil stability, and plant health, making them excellent bioindicators for monitoring ecosystem health and detecting environmental changes. However, challenges such as limited historical data, remote fieldwork, and advanced identification techniques complicate their study. Based on a review of mycological literature and various biodiversity databases, the first inventory of fungi and myxomycetes of the Tehuacán-Cuicatlán Biosphere Reserve (Tehuacán Desert) was prepared in this work. This inventory lists 436 taxa of organisms traditionally identified as fungi, belonging to 254 different genera. Of these, 266 taxa belong to 214 genera of fungi <i>sensu stricto</i>, and 170 taxa from 40 genera of myxomycetes. Fungal and myxomycete communities must be documented, and their inherent variability understood through baseline research. Research on fungal adaptation to shifting environments in the Tehuacán Valley may reveal resilience mechanisms in desert ecosystems. Fungi and myxomycetes are useful bioindicators for assessing ecosystem health and ecological alterations under global climate stress, due to their rapid environmental response. Understanding these adaptive strategies helps preserve the environment, produce new drugs, and foster agricultural resilience. Polyextremotolerant and extremophilic fungi are studied in the reserve to understand the boundaries of life and survival processes. To use fungi to protect sensitive ecosystems and mitigate climate change in the Tehuacán-Cuicatlán Biosphere Reserve, interdisciplinary collaboration and innovative methods are needed. The Tehuacán Desert can be considered a natural laboratory for studying polyextremotolerant and extremophilic fungi.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Profiling of the Microenvironment in High-Risk Neuroblastoma","authors":"Yuxuan Xu,&nbsp;Jinsheng Ding,&nbsp;Zhenyu Shi,&nbsp;Li Bao","doi":"10.1002/iub.70029","DOIUrl":"https://doi.org/10.1002/iub.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>Although tumor biology and treatment of neuroblastoma (NB) have substantially advanced, the clinical outcomes of patients with high-risk NB (HR-NB) still remain unsatisfactory. Increasing evidence suggests that targeting the tumor microenvironment (TME) is an effective strategy for the treatment of patients with HR-NB, highlighting the necessity to deepen the understanding of the complex TME in HR-NB. We analyzed the single-cell RNA sequencing data of 16 NB samples from 11 patients with HR-NB and 5 patients with intermediate-/low-risk NB. We found that proliferating CD8+ <i>TUBA1B</i>+ T cells, <i>H2AFZ</i>+ macrophages, and proliferating <i>HMGB2</i>+ B cells were particularly enriched in HR-NB samples and played an immunosuppressive role. <i>LAG3</i> and <i>HAVCR2</i> could serve as potential immunotherapeutic targets for HR-NB. SCENIC analysis innovatively revealed that proliferating <i>HMGB2</i>+ B cells had a special differentiation process compared with that of plasma cells. <i>H2AFZ</i>+ macrophages evolved from monocytes and M1-like macrophages and exhibited an M2-like phenotype. HR-NB-enriched cancer-associated fibroblasts and endothelial cells were related to tumor migration and progression. An immune-related risk model based on five genes (<i>BIRC5</i>, <i>UBE2C</i>, <i>CDKN3</i>, <i>TK1</i>, and <i>PTTG1</i>) was constructed in the training set and applied to the validation set. Both sets showed a promising clinical prediction value. In sum, this study preliminarily revealed the landscape of the TME in HR-NB at a single-cell level; several TME cell clusters that could inhibit immune activities or promote tumor progression in HR-NB were determined, thereby providing novel immunotherapeutic targets and an immune-related prognostic signature for HR-NB and promoting the development of immunotherapy of HR-NB.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}