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  • Open Access

    ARTICLE

    PpCSC1, a Novel ERD4 Ortholog from Physcomitrium patens, Plays a Negative Role in Salt Stress Tolerance

    Lu Chen1,2,#, Zhijie Ren2,#, Guangmin Zhao2, Xuan He2, Legong Li2, Sheng Teng1,*, Yikun He2,*, Fang Bao2,*

    Phyton-International Journal of Experimental Botany, Vol.95, No.1, 2026, DOI:10.32604/phyton.2025.073817 - 30 January 2026

    Abstract ERD4 proteins, members of the early responsive-to-dehydration family, act as plasma membrane ion channels that contribute to ion homeostasis and modulate plant response to abiotic stresses. However, the functions of ERD4 homologs in non-vascular species remain largely unexplored. Here, we characterized an ERD4 family homolog in Physcomitrium patens (Hedw.) Mitt., PpCSC1 (Calcium-permeable Stress-responsive Cation Channel 1), and investigated its role in salt stress response. PpCSC1 localized to the plasma membrane and functioned as a non-selective cation channel permeable to Na+, K+, Ca2+, and Mg2+. Under salt treatment, PpCSC1 transcripts were markedly downregulated, whereas overexpression lines exhibited enhanced salt sensitivity.… More >

  • Open Access

    ARTICLE

    Integrative Analysis of scRNA-Seq and Bulk RNA-Seq Reveals Novel Transcription Factor Regulating Endothelial Heterogeneity Induced by Lrg1 Following Cerebral Ischemia-Reperfusion

    SHAOFENG XIONG1,2, WENKAI LV3, GUOSHENG CAO4, LONGSHENG FU1, WEN LIU3, MENGFAN LEI2, YANNI LV1,5,*

    BIOCELL, Vol.50, No.1, 2026, DOI:10.32604/biocell.2025.073401 - 23 January 2026

    Abstract Objective: Leucine-rich alpha-2 glycoprotein 1 (Lrg1) could regulate diverse cells in cerebral ischemia-reperfusion. Our study seeks to uncover Lrg1’s impact on endothelial cell heterogeneity via differentiation pathways and transcription factors. Method: The CSOmap model measured cell-to-brain-center distances using single-cell RNA sequencing (scRNA-seq) data in middle cerebral artery occlusion reperfusion (MCAO/R). Monocle2 mapped endothelial differentiation paths. Gene set enrichment analysis (GSEA) analyzed endothelial subcluster variations. Database searches revealed a zinc finger MIZ-type containing 1 protein-frizzled 3 (Zmiz1-Fzd3) promoter interaction. Endothelial cells were transfected with a Fzd3 promoter-luciferase plasmid. Polymerase chain reaction (PCR) and western blotting assessed… More >

  • Open Access

    REVIEW

    The Yin–Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease

    Douglas M. Ruden*

    BIOCELL, Vol.50, No.1, 2026, DOI:10.32604/biocell.2025.072273 - 23 January 2026

    Abstract Stem cell fate decisions are increasingly understood through the dynamic interplay of two fundamental stress-adaptive programs: the integrated stress response (ISR) and the senescence-associated secretory phenotype (SASP). These pathways act as a Yin–Yang system, balancing beneficial and detrimental outcomes across development, tissue homeostasis, and disease. On the yin (protective) side, transient ISR activation and acute SASP signaling foster adaptation, embryonic patterning, wound healing, and regeneration. On the yang (maladaptive) side, chronic ISR signaling and unresolved SASP output drive stem cell exhaustion, fibrosis, inflammation, and tumorigenesis. This duality highlights their roles as both guardians and disruptors More > Graphic Abstract

    The Yin–Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease

  • Open Access

    ARTICLE

    Melatonin and Related Compounds as Enzymatic Antioxidants: A Comprehensive Theoretical Study

    Luis Felipe HernáNdez-Ayala1, Russel J. Reiter2, Annia Galano1,*

    BIOCELL, Vol.50, No.1, 2026, DOI:10.32604/biocell.2025.071635 - 23 January 2026

    Abstract Objectives: Oxidative stress (OS) plays a pivotal role in chronic and neurodegenerative diseases, which has sparked interest in molecules that modulate redox-regulating enzymes. Melatonin and its metabolites exhibit antioxidant properties; however, their molecular mechanisms of enzymatic and transcriptional modulation remain unclear. This study aimed to investigate, through an exploratory in silico approach, the interactions of melatonin and related compounds with OS-related enzymes to generate hypotheses about their role in cellular redox control. Methods: A rational selection of antioxidant, pro-oxidant, and transcriptional targets was performed. Ligands were optimized at the DFT level (M05-2X/6-311+G(d,p)) and docked to OS… More >

  • Open Access

    ARTICLE

    Thimerosal Inhibits Tumor Malignant Progression through Direct Action and Enhancing the Efficacy of PD-1-Based Immunotherapy

    Ping Wang1,2,#, Yan-Han Chen1,2,#, Ze-Tao Zhan1,2, Jun-Xiang Zeng1,2, Yu Chen3,4, Yuan Lin1,2, Tao Chen1,5,*, Wei-Jie Zhou1,2,5,*

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.071902 - 19 January 2026

    Abstract Background: Thimerosal is a mercury-containing preservative widely used in vaccines. This study aimed to investigate its potential antitumor effects and mechanisms in solid malignancies, particularly colorectal cancer (CRC) and melanoma. Methods: A combination of in vitro and in vivo approaches was employed. Cell proliferation, apoptosis, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8), colony formation, ATP viability, Western blotting, flow cytometry, wound-healing and Transwell assays. Subcutaneous, lung metastases, and Azoxymethane/Dextran Sulfate Sodium Salt (AOM/DSS)-induced colitis-associated CRC models were established to examine antitumor efficacy and safety. The functional role of mercury ions was validated using structural… More >

  • Open Access

    ARTICLE

    BHLHE40 Is a Transcriptional Regulatory Target of NFE2L3 in Triple-Negative Breast Cancer

    Shail Rakesh Modi, Terrick Andey*, George Acquaah-Mensah*

    Oncology Research, Vol.34, No.2, 2026, DOI:10.32604/or.2025.070793 - 19 January 2026

    Abstract Objectives: The current treatment options and therapeutic targets for triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer (BrCA), are limited. This study aimed to identify novel biomarkers and transcriptional regulatory networks (TRN) inherent in TNBC samples. Methods: We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas (TCGA) to compare triple-positive breast cancer (TPBC) with TNBC. TRN algorithms and virtual inference of protein-enriched regulon (VIPER) were used to identify master regulators and their target genes. Utilizing TNBC cells (MDA-MB-231 and MDA-MB-468), we validated the relationship of nuclear factor erythroid 2-like 3 (NFE2L3) and… More > Graphic Abstract

    <i>BHLHE40</i> Is a Transcriptional Regulatory Target of <i>NFE2L3</i> in Triple-Negative Breast Cancer

  • Open Access

    ARTICLE

    Biological Features of KLC2 Mutations in Chronic Myeloid Leukemia and Their Contribution to Inducing Drug Resistance

    Rabindranath Bera1,#, Yotaro Ochi2,3, Ying-Jung Huang1, Ming-Chung Kuo1,4, Kenichi Yoshida5, Seishi Ogawa2, Lee-Yung Shih1,4,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070259 - 30 December 2025

    Abstract Background: Breakpoint Cluster Region-Abelson (BCR::ABL1) fusion protein is essential in the pathogenesis of chronic myeloid leukemia (CML); however, the chronic-to-blast phase transformation remains elusive. We identified novel kinesin light chain 2 (KLC2) mutations in CML-myeloid blast phase patients. We aimed to examine the functional role of KLC2 mutations in leukemogenesis. Methods: To evaluate the biological role of KLC2 mutants (MT) in CML cells, we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot, immunofluorescence, cell proliferation, differentiation, and apoptosis; Tyrosine kinase inhibitor (TKI)-drug activities; and clonogenic assays for in vitro functional analyses. We co-expressed KLC2-MTMore >

  • Open Access

    ARTICLE

    ETV4-Mediated PD-L1 Upregulation Promotes Immune Evasion and Predicts Poor Immunotherapy Response in Melanoma

    Tao Zhu1, Taofeng Wei1, Mingdong Yang1, Junjun Xu1, Huifang Jiang1, Wei He1, Juyan Zheng2,*, Haibin Dai1,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.070180 - 30 December 2025

    Abstract Background: Aberrant expression of transcription factors (TFs) is a key mechanism mediating tumor immune escape and therapeutic resistance. The involvement of E26 transformation-specific (ETS) family of TFs in immune regulation is not fully understood. The study aimed to elucidate the function of E-twenty-six variant 4 (ETV4) in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma. Methods: The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma (HCC). Single-cell RNA sequencing (scRNA-seq) was used to dissect the cellular expression and function of ETV4 in the tumor… More >

  • Open Access

    ARTICLE

    ELK4 Promotes Vasculogenic Mimicry in Oral Squamous Cell Carcinoma via Driving DHFR Transcriptional Activation

    Yongle Qiu1,#, Kunshan Li1,#, Wenjing Wang1, Wenjuan Zhang2, Jilun Liu2, Yang Bai3, Fei Xu3, Jie Guo1,*

    Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.069612 - 30 December 2025

    Abstract Background: The regulatory mechanisms governing vasculogenic mimicry (VM) in oral squamous cell carcinoma (OSCC) remain largely undefined. This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC. Methods: Bioinformatics analysis was performed utilizing single-cell RNA-seq, bulk RNA-seq, and histone H3 lysine 27 acetylation (H3K27ac) Chromatin Immunoprecipitation (ChIP)-seq data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4 (ELK4) to the dihydrofolate reductase (DHFR) enhancer. In vitro VM formation and invasion of OSCC cells were… More > Graphic Abstract

    ELK4 Promotes Vasculogenic Mimicry in Oral Squamous Cell Carcinoma via Driving <i>DHFR</i> Transcriptional Activation

  • Open Access

    REVIEW

    Key Plant Transcription Factors in Crop Tolerance to Abiotic Stresses

    Nadia Lamsaadi1, Oumaima Maarouf2, Soukaina Lahmaoui2, Hamid Msaad2, Omar Farssi2, Chaima Hamim2, Mohamed Tamoudjout2, Hafsa Hirt2, Habiba Kamal2, Majida El Hassni2, Cherki Ghoulam3,4, Ahmed El Moukhtari5,*, Mohamed Farissi2

    Phyton-International Journal of Experimental Botany, Vol.94, No.11, pp. 3585-3610, 2025, DOI:10.32604/phyton.2025.072311 - 01 December 2025

    Abstract Abiotic stresses, such as drought, heavy metals, salinity, and extreme temperatures, are among the most common adverse threats that restrict the use of land for agriculture and limit crop growth and productivity. As sessile organisms, plants defend themselves from abiotic stresses by developing various tolerance mechanisms. These mechanisms are governed by several biochemical traits. The biochemical mechanisms are the products of key genes that express under specific conditions. Interestingly, the expression of these genes is regulated by specialized proteins known as transcription factors (TFs). Several TFs, including those from the bZIP, bHLH, MYB, HSF, WRKY,… More >

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