Biological Research最新文献

{"title":"Reelin regulates the migration and differentiation of extravillous trophoblastic cells.","authors":"Nicole Sommer, Carlos Alarcon-Godoy, Héctor Pizarro, Aníbal Pacheco, Jorge A Carvajal, Hugo Olguín, Jaime Gutiérrez, Andrea Leiva, María-Paz Marzolo","doi":"10.1186/s40659-026-00690-1","DOIUrl":"10.1186/s40659-026-00690-1","url":null,"abstract":"<p><p>BACKGROUND: ApoER2/LRP8 is a receptor highly expressed in the placenta; however, its physiological role in this organ remains poorly understood. The VLDL receptor has been less studied in the placenta. Reelin, a relevant ligand for both receptors, is an extracellular glycoprotein that participates in neuronal polarization, migration and differentiation, hence having a central role in the central nervous system (CNS) development. Reelin triggers a complex signaling pathway that regulates cytoskeleton dynamics, cell migration, differentiation and gene expression. This paper aimed to determine whether the Reelin signaling pathway plays a role in cellular processes involved in placentation. RESULTS: Reelin receptors ApoER2 and VLDLR were found in first-trimester extravillous trophoblast (EVT) cell lines. EVT cells Swan 71 responded to Reelin exposure by activating PI3K-Akt and increasing ApoER2 protein levels, but not VLDLR. Additionally, a dual role for Reelin via PI3K was established in these cells, as it enhanced trophoblastic migration at 2% O2 (to mimic the hypoxic physiologic conditions of trophoblastic migration) and promoted differentiation to an endothelial-like phenotype at 21% O2. Migration was also stimulated, independent of PI3K, when cells were exposed to normoxic (21% O2) or chemically induced hypoxic (CoCl2) conditions. We propose that, physiologically, during the first trimester, Reelin, together with its receptors, could stimulate trophoblastic migration and differentiation. Interestingly, under hypoxia, ApoER2 and VLDLR protein levels were increased, and Reelin modulated hypoxia-inducible factor HIF1-α levels. ApoER2, VLDLR and Reelin were detected in human term placentas from normal and pre-eclampsia with severe features (PE-SF) pregnancies. In the plasma of first-trimester pregnant women, Reelin levels were lower in patients with severe preeclampsia (PE) at a time before the onset of PE clinical symptoms. CONCLUSIONS: Reelin could be involved in placentation, playing roles in EVT migration and differentiation. The reduction in maternal Reelin levels detected early in pregnancy could be a potential biomarker for PE. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520077","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":"Changes in the microRNA cargo of granulosa cell-derived extracellular vesicles under oxidative stress in a bovine model.","authors":"Judith Diaz-Muñoz, Yulia N Cajas, Karina Cañón-Beltrán, Lena Arévalo, Sonia Gago, María Iniesta-Cuerda, Ana Josefa Soler, Dimitrios Rizos, Teresa Mogas","doi":"10.1186/s40659-026-00689-8","DOIUrl":"10.1186/s40659-026-00689-8","url":null,"abstract":"<p><p>BACKGROUND: Granulosa cells (GCs) play a central role in oocyte maturation and follicular development, and their function is very sensitive to oxidative stress, which can compromise female fertility. Extracellular vesicles (EVs) released by GCs serve as intercellular messengers and are known to carry bioactive molecules, including microRNAs (miRNAs), which can modulate stress responses and cellular communication within the follicular environment. Understanding the molecular mechanisms underlying oxidative stress responses in reproductive tissues is crucial for improving fertility. This study aimed to characterize and compare the miRNA profiles of both GCs and their secreted EVs following exposure to oxidative stress. Bovine GCs were treated with 5 µM H2O2 for 40 min, followed by 24 h of culture. EVs were isolated from the conditioned media using size-exclusion chromatography and characterized by nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry. Small RNA sequencing was performed on both the GCs and their secreted EVs to identify stress-responsive miRNA signatures. RESULTS: Exposure to oxidative stress increased intracellular ROS levels and decreased mitochondrial activity in GCs, confirming successful stress induction. Differential expression analysis revealed no significant changes in miRNA abundance in GCs in response to oxidative stress, suggesting cellular adaptation mechanisms that preserve intracellular miRNA homeostasis. In GC derived EVs, however, 10 miRNAs were significantly more abundant, including miR-134, miR-10175-5p, miR-197, miR-2284 h-5p, miR-2284y, miR-2285av, miR-2285au, miR-369-5p, miR-2411-5p and miR-2387. These miRNAs showed log2 fold changes ranging from 3.57 to 6.89 compared to control, indicating substantial enrichment in stress-derived EVs. Functional enrichment analysis of predicted targets for the higher abundant EV-miRNAs revealed involvement in processes such as angiogenesis, cell migration as well as WNT, MAPK and Oxytocin signaling pathways, all critical for follicular function and stress adaptation. CONCLUSIONS: These findings suggest that oxidative stress alters the miRNA cargo of EVs, potentially affecting intra-follicular communication and stress adaptation The selective packaging of specific miRNAs into EVs under stress conditions indicates a sophisticated cellular mechanism for intercellular communication during adverse conditions. This dual characterization provides new insights into the regulatory role of EV-derived miRNAs in ovarian physiology under oxidative conditions and establishes the foundation for developing EVs-miRNAs as potential biomarkers for reproductive health assessment. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509180","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":"The progress and challenges of mesenchymal stromal cell-based therapy for diabetes and its complications.","authors":"Leyi Tu, Tianyun Gao, Pingping Shen, Bin Wang","doi":"10.1186/s40659-026-00687-w","DOIUrl":"10.1186/s40659-026-00687-w","url":null,"abstract":"<p><p>BACKGROUND: Diabetes, a metabolic disorder characterized by chronic hyperglycemia resulting from insulin deficiency or resistance, continues to pose significant global health challenges with rising morbidity and mortality rates. While current therapies provide symptomatic management, they fail to address the underlying pathophysiology or prevent disease progression. Mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic approach due to their unique triad of capabilities: multilineage differentiation potential, self-renewal capacity, and potent immunomodulatory properties. Through sophisticated paracrine mechanisms, MSCs exert multifaceted therapeutic effects including angiogenesis promotion, anti-inflammatory action, tissue regeneration, and immune system regulation, positioning them as ideal candidates for diabetes intervention. SCOPE OF REVIEW: This comprehensive review provides three novel contributions to the field: (1) First systematic comparison of MSC tissue sources, including umbilical cord (UC-MSCs), bone marrow (BM-MSCs) and Wharton's jelly (WJ-MSCs), for diabetes treatment efficacy; (2) Critical analysis of recently developed MSC engineering techniques to enhance therapeutic outcomes; (3) Original synthesis of optimal delivery protocols for specific diabetic complications including diabetic wounds (DW), nephropathy (DNp), retinopathy (DR), neuropathy (DNe), and cardiomyopathy (DCM). Our analysis incorporates the most recent clinical trial data (2020–2023) not covered in previous reviews. MAJOR CONCLUSIONS: Combined with preclinical studies and clinical trials, MSC therapy demonstrates significant safety and efficacy. However, therapeutic durability remains limited, with efficacy declining by 40–60% after 6 months in most trials. This raises significant questions about its long-term clinical impact. This limitation stems primarily from poor cell engraftment and compromised survival and function within the hostile diabetic microenvironment, which is characterized by chronic inflammation, oxidative stress, and endoplasmic reticulum stress. Emerging solutions include: (1) MSC preconditioning with hypoxia; (2) Biomaterial encapsulation; and (3) Genetic modification for targeted delivery. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466615","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":"Substitution of the SEMA3A basic domain with the VEGF₁₆₅ heparin-binding domain enhances anti-angiogenic potency in ovo.","authors":"Indrė Valiulytė-Simaitė, Lina Šlekienė, Ingrida Balnytė, Viktorija Daukšaitė, Saulius Tacionis, Gabrielė Paškevičiūtė, Kristina Mašalaitė, Arūnas Kazlauskas","doi":"10.1186/s40659-026-00684-z","DOIUrl":"10.1186/s40659-026-00684-z","url":null,"abstract":"<p><p>BACKGROUND: Angiogenesis plays a critical role in tumor development, with neuropilin receptors (NRPs) involved in this process through their interactions with vascular endothelial growth factor (VEGF) and semaphorins. SEMA3A, a member of class 3 semaphorins, demonstrates strong antiangiogenic potential. In this study, the C-terminal basic domain of SEMA3A was replaced with the heparin-binding domain (HBD) of VEGF165, hypothesizing that the resultant chimeric protein SEMA-PSI-IG-HBD would enhance antiangiogenic efficacy by: (1) competing with VEGF for NRPs (2) utilizing the HBD as a molecular anchor to increase the residence time and local concentration of the hybrid within the tumor microenvironment. METHODS: To assess the effects of SEMA-PSI-IG-HBD on angiogenesis, a series of in vitro assays including microcapillary network formation, 3D cell spheroid sprouting, proliferation and interaction with NRP1 were carried out, whereas in ovo experiments were performed by using the chicken embryo chorioallantoic membrane (CAM) model. RESULTS: Pull-down assays confirmed that the SEMA-PSI-IG-HBD hybrid specifically interacted with secreted NRP1 in a manner similar to the wild-type SEMA3A, validating the structural integrity of the chimeric protein’s receptor-binding interface. SEMA-PSI-IG-HBD and SEMA3A showed comparable inhibition in 2D microcapillary formation and 3D spheroid sprouting assays. However, the hybrid demonstrated markedly superior anti-angiogenic activity in the complex 3D environment of the CAM model. CONCLUSIONS: Our findings demonstrate that by combining competitive occupancy of NRP1 with potent anti-angiogenic signaling, SEMA-PSI-IG-HBD represents a promising therapeutic candidate for the regulation of pathological vascularization in cancer. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147466658","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":"Phosphorus and cold stress: physiological and biochemical assessment in two grape (Vitis vinifera L.) cultivars.","authors":"Maryam Zaeri-Behrooz, Rouhollah Karimi, Ali Khadivi, Yazgan Tunç","doi":"10.1186/s40659-026-00683-0","DOIUrl":"10.1186/s40659-026-00683-0","url":null,"abstract":"<p><p>Low temperature is one of the most damaging factors in the production of horticultural crops. This study was conducted to investigate the mechanisms of frost tolerance resulting from the use of different concentrations of phosphorus (P) fertilizer in two grape (Vitis vinifera L.) cultivars, ‘Khalili’ and ‘Perlette’, factorially based on a completely randomized design on potted vines. The cultivars were treated with a Hoagland nutrient solution containing three different P concentrations (0, 0.5, and 1 mM), and were examined at two temperatures, 24 °C and 2 °C. The results showed that cold tolerance was higher in the ‘Khalili’ cultivar compared with the ‘Perlette’ cultivar. In both cultivars, the samples treated with 1 mM P concentration exhibited the lowest values for cold tolerance-related indices. The highest cold tolerance, measured using the electrolyte leakage method, was observed in the ‘Khalili’ cultivar at 0.5 mM P concentration. The highest amounts of hydrogen peroxide and malondialdehyde were observed at 0 and 1 mM P concentrations under the + 2 °C temperature treatment. The lowest activity of antioxidant enzymes, soluble sugars, soluble proteins, and polyamines was observed at a 1 mM P concentration in both ‘Khalili’ and ‘Perlette’ cultivars. In this treatment, the lowest amounts of chlorophyll, anthocyanins, and leaf calcium, magnesium, zinc, copper, and active iron were observed. The ratio of active iron to total iron significantly decreased at the 1 mM P concentration, and leaf chlorosis was visible in this treatment. These results indicate that optimum concentrations of P (0.5 mM) can physiologically and biochemically lead to improved cold tolerance of grapevine plants.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455470","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":"Isoimperatorin suppresses triple-negative breast cancer by modulating miR-874-3p/POU2F1 axis: a new avenue for metabolic and redox intervention.","authors":"Shuo Wu, Yuexuan Su, Ruishan Zhang, Yuying Wang, Xiang Li","doi":"10.1186/s40659-026-00678-x","DOIUrl":"10.1186/s40659-026-00678-x","url":null,"abstract":"<p><p>BACKGROUND: Metabolic alterations are key factors driving the development of breast cancer. Among them, metabolic reprogramming is an important biological hallmark of breast cancer. It is crucial to gain in-depth understanding of the relevant mechanisms and find effective treatment strategies. Isoimperatorin (ISO), a natural furanocoumarin, exhibits various pharmacological effects such as anti-inflammatory and antiviral activities. However, the impact of ISO on the growth of breast cancer cells and its underlying mechanisms remain unclear. METHODS: Cell culture, transfection, and animal experiments were employed. CCK -8, colony formation, and flow cytometry were used to detect cell proliferation, apoptosis, and ROS levels. miRNA-Seq, qRT-PCR, and Western Blotting were applied to analyze gene and protein expression. RESULTS: ISO inhibited breast cancer cell proliferation, induced apoptosis and ROS accumulation, and suppressed the Warburg effect. ISO upregulated miR- 874-3p, which directly targeted the 3′-UTR of POU2F1, inhibiting the transcriptional activation of key glycolytic genes. Blocking this axis reversed ISO’s tumor-suppressive effects in vitro and in vivo. CONCLUSION: This study first reveals a novel mechanism by which ISO regulates breast cancer metabolism and apoptosis via the miR-874-3p/POU2F1 axis, highlighting ISO’s potential as a dual metabolic-redox intervention agent and providing a new combined therapeutic target for breast cancer. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442779","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":"DNA damage and cell death induced by exposure to ultra-high dose rate low-dose pulsed X-rays emitted from a kilojoule plasma focus device.","authors":"Héctor Araya, Jalaj Jain, Rodrigo Andaur, José Moreno, Sergio Davis, Pablo Diaz, Ethel Velásquez, Josefa Orellana, Martín Ríos, Jessica Toro, Octavio Orellana-Serradell, Cristopher Fierro, Leopoldo Soto, Katherine Marcelain","doi":"10.1186/s40659-026-00674-1","DOIUrl":"10.1186/s40659-026-00674-1","url":null,"abstract":"<p><p>BACKGROUND: FLASH radiotherapy, characterized by ultra-high dose rates (> 40 Gy/s), potentially spares normal tissues while maintaining antitumor efficacy (the FLASH effect). While electron and proton FLASH are explored, pulsed X-ray sources like plasma focus devices offer unique possibilities. Previous work has reported hyper-radiosensitivity in colorectal cancer cells exposed to ultra-high-dose-rate pulsed X-rays from a kilojoule plasma focus (PF) device, without significant effects on non-cancerous cells. This study further investigates the biological effects of ultra-high-dose-rate (~ 10⁷ Gy/min), low-total-dose pulsed X-rays generated by a PF-2 kJ device on colorectal cancer cell lines, focusing on DNA damage, cell cycle progression, and gene expression. RESULTS: Low-total-dose (~ 0.25 Gy), ultra-high-dose-rate pulsed X-rays (0.025 Gy/pulse, a total of 10 pulses, pulses temporally separated by 15–20 s) generated by a PF-2 kJ device induced a significant increase in the SubG1 population in HCT116 and DLD1 cells over 72 h, an effect indicative of apoptosis, which was not observed with conventional X-rays at similar total doses. In addition, pulsed X-rays induced apoptosis in radioresistant MCF-7 breast cancer cells. Whereas conventional X-rays did not cause a significant increase in double-strand breaks (DSBs), surrogate marker γ-H2AX and phosphor-P53(Ser15) signal were detected 30 min following pulsed X-ray exposure and persisted for up to 24 h, and no evidence of G2/M cell cycle arrest was detected in exposed cells. Gene expression analysis and preliminary transcriptomic data further suggest a DNA damage response leading to cell death and global change in general biological processes related to regulation of gene expression. CONCLUSION: Low-total-dose (~ 0.25 Gy), ultra-high-dose-rate pulsed X-rays generated by a PF-2 kJ device induce significant and sustained DNA damage (DSBs) leading to increased apoptosis in colorectal (HCT-116, DLD-1) and breast (MCF-7) cancer cells, compared to conventional X-rays. These effects, coupled with distinct changes in gene expression, suggest that ultra-high-dose-rate pulsed X-rays may overcomeradio-resistancee without eliciting a conventional DNA damage repair or cell cycle checkpoint response. These findings support the potential of PF-generated pulsed X-rays as a novel sourcof e radiotherapy modality and warrant further investigation, particularly in in vivo models, to assess clinical applicability and safety. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430909","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":"Smarce1-dependent modulation of Stat3 signaling governs cardiomyocyte proliferation.","authors":"Deung-Dae Park, Alena Boos, Antonia Hermann, Sujin Kim, Wolfgang Rottbauer, Steffen Just","doi":"10.1186/s40659-026-00681-2","DOIUrl":"10.1186/s40659-026-00681-2","url":null,"abstract":"<p><p>Developmental pathways that govern organ growth during embryogenesis are often reactivated in adult organisms to support tissue regeneration. Despite their profound clinical relevance for cardiac repair, the molecular mechanisms underlying heart growth during development and regeneration remain incompletely understood. Here, we identify Smarce1, a core subunit of the SWI/SNF chromatin-remodeling complex, as a key regulator of cardiomyocyte (CM) proliferation in zebrafish. Using genetically engineered Smarce1 loss-of-function models, we combined heart-specific transcriptomic (RNA-seq, single-cell RNA-seq) and epigenomic (ATAC-seq) profiling to delineate Smarce1-dependent regulatory networks. Smarce1 deficiency enhanced CM proliferative activity by modulating cell cycle dynamics and chromatin accessibility. Integrative analyses revealed that Smarce1 regulates the transcriptional landscape of Stat3 signaling components, thereby linking chromatin remodeling to proliferative signaling. Genetic and pharmacological modulation of Stat3 signaling confirmed its functional contribution to Smarce1-dependent CM proliferation, establishing a conserved Smarce1-Stat3 axis operating during both developmental and adult cardiac growth. Collectively, our findings uncover an epigenetic mechanism by which Smarce1 fine-tunes CM proliferation and identify Smarce1 as a promising target for promoting regenerative CM expansion.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430902","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":"Concurrent high-intensity interval plus resistance training improves vascular health in breast cancer survivors with high chemotherapy exposure.","authors":"Cristian Álvarez, Carolina Fuentes, Cristóbal Durán-Marín, Pedro Delgado-Floody, Gabriel Rojas-Rojas, Manuel Gomez, Alvaro N Gurovich, David C Andrade","doi":"10.1186/s40659-026-00677-y","DOIUrl":"10.1186/s40659-026-00677-y","url":null,"abstract":"<p><p>BACKGROUND: The aim was to determine the effects of 8 weeks of concurrent training of abbreviated high-intensity interval-training and low–load resistance training (CTHIIT+RT) on functional and structural vascular outcomes of breast cancer survivors with a history of high or low exposure to chemotherapy sessions. METHODS: Breast cancer survivor women (n = 21, 58.7 ± 8.7 years) were divided into high– (HVchemo, n = 11) or low–volume chemotherapy groups (LVchemo, n = 10). Pulse wave velocity (PWV) and carotid intima–media maximum (cIMTmax) were the primary outcomes, while flow-mediated dilation (FMD), carotid intima–media average (cIMTav), baseline brachial artery diameter (Dbase), peak diameter (Dpeak), and one-repetition maximum tests for the biceps (1RMbc), shoulder (1RMsp), back (1RMback), and leg extension (1RMLeg) served as secondary outcomes. RESULTS: PWV decreased in the LVchemo group (∆˗1.64 m⋅s− 1, p < 0.001) but not in the HVchemo group. cIMTmax was reduced only in the HVchemo group (∆˗0.23 mm, p = 0.024). FMD was significantly increased in the HVchemo (∆+5.06%, p = 0.023) but not in the LVchemo group. HVchemo and LVchemo groups increased Dbase (∆+0.38 mm, p = 0.005; and ∆+0.16 mm, p < 0.0001) and Dpeak (∆+0.32 mm, p = 0.008; and ∆+0.12 mm, p < 0.0001). HVchemo and LVchemo groups increase 1RMbc (∆+2.3 kg; and ∆+2.09 kg), 1RMsp (∆+2.15 kg; and ∆+2.36 kg), 1RMback (∆+4.4 kg; and ∆+4.58 kg), and 1RMLeg (∆+6.15 kg; and ∆+5.27 kg), all p < 0.01. CONCLUSIONS: Eight weeks of CTHIIT+RT in women breast cancer survivors who received higher chemotherapy volume reduces cIMTmax, but increases FMD, Dbase, Dpeak, cardiorespiratory fitness, and muscle strength. Vascular improvements were partially observed in subjects with lower chemotherapy volumes. </p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276016","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":"The polyamine inhibitor SAM486A increases the efficacy of adagrasib in non-small cell lung cancer cells harboring KRAS^G12C mutation.","authors":"Antonia Martin-Martin, Carina Chipón, Constanza Guzman-Kunstmann, Sergio Guzman-Kunstmann, Neudo Buelvas, Claudio Henríquez, Francisca Vidal, Franz Villarroel-Espindola, Trista K Hinz, Lynn E Heasley, Rodrigo A López-Muñoz","doi":"10.1186/s40659-026-00679-w","DOIUrl":"10.1186/s40659-026-00679-w","url":null,"abstract":"<p><strong>Background: </strong>Non-small cell lung cancer (NSCLC) accounts for most lung cancer cases and poses major challenges due to late-stage diagnosis and limited options. A substantial subset of NSCLC harbors KRAS mutations, most commonly at codon 12. Although KRAS^G12C inhibitors show clinical activity, their efficacy is frequently limited by acquired resistance. Polyamines (putrescine, spermidine, and spermine) regulate key cellular processes and are dysregulated during tumorigenesis. S-adenosylmethionine decarboxylase 1 (AMD1) inhibitors such as SAM486A reduce tumor cell proliferation and migration. Thus, we evaluated the combination of the KRAS^G12C inhibitor adagrasib with SAM486A in KRAS^G12C-mutant NSCLC, in vitro and in vivo.</p><p><strong>Methods: </strong>In vitro assays included viability (MTT), clonogenic, BrdU incorporation, and Western blot analyses across four NSCLC cell lines. Drug-drug interactions were quantified using Combenefit software. In vivo efficacy was tested in C57BL/6 mice using an orthotopic model with LLC46 (KRAS^G12C/NRAS^KO) cells and a metastatic model with LL2 (KRAS^G12C/NRAS^Q61H) cells. Tumor growth was monitored by µCT or caliper measurements, and immunohistochemistry (PCNA) was used to assess proliferation.</p><p><strong>Results: </strong>In vitro, adagrasib reduced AMD1 levels, and SAM486A synergistically enhanced its antiproliferative effects, particularly in KRAS^G12C-mutant cell lines, with minimal effects on KRAS-wild-type cells. In an orthotopic mouse model using a KRAS^G12C/NRAS^KO NSCLC line, the combination provided minimal additional benefit over adagrasib monotherapy. In a metastatic model, however, the combination reduced tumor size and PCNA staining more than either monotherapy.</p><p><strong>Conclusions: </strong>Our results suggest that targeting polyamine metabolism with SAM486A enhances the efficacy of KRAS^G12C inhibitors and may mitigate resistance. This combination represents a promising therapeutic approach for KRAS^G12C-mutant NSCLC and warrants further clinical investigation.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225578","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}