IF 6 2区生物学

Cells Pub Date : 2026-10-02 DOI: 10.3390/cells15191803

John J Alam, Ursula A Germann, Paul Maruff

{"title":"Targeting Pro-Inflammatory Interleukin-1 Beta Signaling to Modulate Neuroinflammatory Processes Associated with Cognitive Decline in Dementia with Lewy Bodies.","authors":"John J Alam, Ursula A Germann, Paul Maruff","doi":"10.3390/cells15191803","DOIUrl":"10.3390/cells15191803","url":null,"abstract":"Interleukin-1 beta (IL-1β) is implicated as a molecular driver of cognitive decline in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), potentially through activation of pro-inflammatory pathways within the neuron that impair synaptic function. Because pro-inflammatory IL-1β signaling depends on p38α kinase, the oral brain-penetrant p38α inhibitor neflamapimod has the potential to reverse synaptic dysfunction and treat cognitive decline in these contexts. Neflamapimod has also shown positive effects in animal models and in clinical studies in AD and DLB. Herein we evaluated neflamapimod effects on pro-inflammatory IL-1β signaling in vitro and in patients with AD or DLB. In human PBMCs, neflamapimod inhibited IL-1β-induced IL-6 and IL-8 production with EC50 values of 6.3 ± 1.3 nM and 7.1 ± 3.2 nM, respectively. In AD, six weeks of neflamapimod 40 mg BID treatment reduced CSF levels of IL-6 and IL-8, with maximal effects at trough drug concentration ≥4 ng/mL (9 nM). In DLB, neflamapimod 40 mg TID increased the plasma Aβ42/40 ratio and reduced plasma GFAP levels, treatment effects consistent with reduced pro-inflammatory IL-1β signaling. Collectively, these results support the hypothesis that inhibition of p38α-dependent IL-1β signaling may beneficially modulate neuroinflammatory processes that otherwise are associated with cognitive decline in DLB, and potentially in AD.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191601","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

Molecular Architecture of the H2AX-Containing Nucleosome from Arabidopsis. 拟南芥含h2ax核小体的分子结构。

IF 6 2区生物学

Cells Pub Date : 2026-10-01 DOI: 10.3390/cells15191795

Rashmi Panigrahi, Ross Edwards, Nathaniel Agbagba, Mark Glover

{"title":"Molecular Architecture of the H2AX-Containing Nucleosome from Arabidopsis.","authors":"Rashmi Panigrahi, Ross Edwards, Nathaniel Agbagba, Mark Glover","doi":"10.3390/cells15191795","DOIUrl":"10.3390/cells15191795","url":null,"abstract":"Nucleosomes integrate diverse histone variants to organize chromatin and coordinate genome maintenance. In plants, the structural interplay between replication-associated histones and DNA damage-responsive histone variants remains poorly understood. Here, we determine cryogenic electron microscopy structures of an Arabidopsis thaliana (At) nucleosome containing the replication-associated histones H2B.6 and H3.1 together with the DNA damage-responsive variant H2AXa. The mononucleosome structure, resolved at 2.73 Å, preserves the canonical nucleosome architecture. Unexpectedly, the reconstituted mononucleosomes formed defined higher-order assemblies in the absence of linker DNA or chemical crosslinking. Two distinct nucleosome-nucleosome arrangements, parallel and right offset, were identified. The right offset closely resembles the human counterpart, whereas the parallel arrangement exhibits slight displacement of H2B structural elements at the inter-nucleosomal interface. Together these structures reveal how a distinct histone composition preserves the canonical nucleosome architecture while supporting multiple defined modes of nucleosome packing, providing structural insights into conserved and divergent features of H2AX-containing chromatin organization across plants and animals.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191555","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

Salivary miR-21 and miR-31 in Oral Squamous Cell Carcinoma: Molecular Pathogenesis, Diagnostic Significance, and Translation to Isothermal RPA. 唾液miR-21和miR-31在口腔鳞状细胞癌中的分子发病机制、诊断意义和向等温RPA的转化。

IF 6 2区生物学

Cells Pub Date : 2026-10-01 DOI: 10.3390/cells15191799

Jyotsna S Ranbhise, Manish Kumar Singh, Hyeong Rok Yun, Sunhee Han, Sung Soo Kim, Insug Kang

{"title":"Salivary miR-21 and miR-31 in Oral Squamous Cell Carcinoma: Molecular Pathogenesis, Diagnostic Significance, and Translation to Isothermal RPA.","authors":"Jyotsna S Ranbhise, Manish Kumar Singh, Hyeong Rok Yun, Sunhee Han, Sung Soo Kim, Insug Kang","doi":"10.3390/cells15191799","DOIUrl":"10.3390/cells15191799","url":null,"abstract":"Oral Squamous Cell Carcinoma (OSCC) is often diagnosed at advanced stages despite the oral cavity's anatomical accessibility, highlighting the need for molecular adjuncts that can identify disease-associated changes before overt morphological progression. This review evaluates the biological roles and salivary diagnostic potential of microRNA-21 (miR-21) and miR-31, two miRNAs repeatedly associated with OSCC pathogenesis and progression. We examine current clinical evidence supporting their use as salivary biomarkers and discuss major sources of methodological variability, including differences in saliva collection, RNA recovery, normalization, and diagnostic thresholds. We pay particular attention to the transition from laboratory-based RT-qPCR to Recombinase Polymerase Amplification (RPA) for decentralized detection. Although RPA offers rapid, low-temperature amplification with reduced hardware requirements, mature miRNAs present a key technical challenge because their short length requires prior target extension or conversion. Successful chairside translation will depend on standardized sample processing, robust target-specific amplification, contamination control, and validation in clinically relevant early-stage and comparator populations.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191493","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

Motor Neuron Disease in a Dish: The Power of Human Induced Pluripotent Stem Cell-Derived Spinal Motor Neurons and Glial Cells. 培养皿中的运动神经元疾病：人类诱导多能干细胞衍生的脊髓运动神经元和神经胶质细胞的力量。

IF 6 2区生物学

Cells Pub Date : 2026-10-01 DOI: 10.3390/cells15191798

Martina Morrone, Chiara F Valori, Liliana Brambilla, Daniela Rossi

{"title":"Motor Neuron Disease in a Dish: The Power of Human Induced Pluripotent Stem Cell-Derived Spinal Motor Neurons and Glial Cells.","authors":"Martina Morrone, Chiara F Valori, Liliana Brambilla, Daniela Rossi","doi":"10.3390/cells15191798","DOIUrl":"10.3390/cells15191798","url":null,"abstract":"Induced pluripotent stem cells (iPSCs) have revolutionized disease modelling by providing unprecedented opportunities to investigate complex human disorders. Among others, Amyotrophic Lateral Sclerosis (ALS), the most common adult-onset motor neuron disease, clearly embodies this complexity. This disorder remains particularly challenging not only because of its marked clinical and molecular heterogeneity but also as a consequence of the composite interactions between motor neurons and the neighboring non-neuronal cells, especially astrocytes, which contribute to disease progression. The ability to generate patient-specific spinal motor neurons and astrocytes from human iPSCs has enabled the development of in vitro models that recapitulate key pathological features of ALS, offering valuable platforms to investigate disease mechanisms, to identify therapeutic targets, and to support personalized medicine approaches. In this review, we summarize current iPSC-based strategies for modelling ALS, highlighting their applications in studying disease physiopathology and drug development. In addition, advanced human iPSC-derived technologies, including organoids and organ-on-a-chip systems, are discussed highlighting their potential, current limitations, and future perspectives.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191565","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 Gut Microbiota-Immunity Axis in Colorectal Cancer: Implications for Immunotherapy and Clinical Translation. 结肠直肠癌的肠道微生物-免疫轴：免疫治疗和临床转化的意义。

IF 6 2区生物学

Cells Pub Date : 2026-10-01 DOI: 10.3390/cells15191800

Izabela Siemińska

{"title":"The Gut Microbiota-Immunity Axis in Colorectal Cancer: Implications for Immunotherapy and Clinical Translation.","authors":"Izabela Siemińska","doi":"10.3390/cells15191800","DOIUrl":"10.3390/cells15191800","url":null,"abstract":"Colorectal cancer (CRC) arises within a complex microbial ecosystem that may influence carcinogenesis, tumor immunity, and therapeutic response. This is particularly relevant in metastatic disease, where most tumors are microsatellite-stable/mismatch repair-proficient (MSS/pMMR) and derive little meaningful benefit from immune checkpoint inhibitor (ICI) monotherapy. Specific pathobionts, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, have been implicated in genotoxic, inflammatory, and checkpoint-related mechanisms that may contribute to tumor progression and immune evasion, whereas selected commensals and microbiota-derived metabolites may support antitumor immunity in a context-dependent manner. This review integrates translational evidence linking microbial taxa and functions, metabolites, neutrophil biology, bacterial extracellular vesicles, and T-cell dysfunction with CRC progression and immunotherapy response. This review critically examines emerging microbiome-directed strategies, including fecal microbiota transplantation, next-generation probiotics, defined bacterial consortia, dietary and perioperative interventions, postbiotics, and bacteriophage-based approaches, as potential means of modifying immune resistance in MSS/pMMR CRC. Although early clinical signals from microbiota-modulating combinations are encouraging, the available evidence remains limited by small cohorts, heterogeneous interventions, and the absence of randomized CRC-specific studies. Microbiome-based biomarkers and therapeutics therefore remain investigational, and standardized sampling, prospective validation, and carefully designed trials will be required before microbiome modulation enters routine CRC care.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191622","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

NGAL as a Biomarker of Tubular Injury and Glomerular Dysfunction in Fabry Nephropathy. 法布里肾病肾小管损伤和肾小球功能障碍的生物标志物。

IF 6 2区生物学

Cells Pub Date : 2026-10-01 DOI: 10.3390/cells15191797

Margarita M Ivanova, Julia Dao, Leah Svarny, Emily Nguyen, Sahithi Ponnam, Ozlem Goker-Alpan

{"title":"NGAL as a Biomarker of Tubular Injury and Glomerular Dysfunction in Fabry Nephropathy.","authors":"Margarita M Ivanova, Julia Dao, Leah Svarny, Emily Nguyen, Sahithi Ponnam, Ozlem Goker-Alpan","doi":"10.3390/cells15191797","DOIUrl":"10.3390/cells15191797","url":null,"abstract":"Fabry disease (FD) is an X-linked lysosomal disorder caused by pathogenic variants in the GLA gene, resulting in α-galactosidase A deficiency and accumulation of Gb3/lyso-Gb3 (globotriaosylceramide/globotriaosylsphingosine) in cells, including podocytes and renal tubular cells. While podocyte damage drives glomerular dysfunction, tubular dysfunction leads to atrophy and fibrosis, often preceding a detectable decline in glomerular filtration rate (eGFR). Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of renal injury, with urinary and plasma NGAL reflecting distinct aspects of renal dysfunction; however, their clinical value in Fabry nephropathy (FN) remains poorly defined. We explored the clinical relevance of NGAL in distinguishing tubular atrophy from glomerular podocytopathy. Thirty-three FD patients were categorized into groups without and with FN using eGFR. In males, elevated NGAL strongly correlated with FN. In females, urine NGAL was increased regardless of nephropathy status, while plasma NGAL rose mainly in those with reduced eGFR. This pattern suggests that tubular damage and early tubulointerstitial fibrosis (TIF) may precede glomerular impairment in female patients. Conclusions: Tubular damage may precede glomerular dysfunction in FD, and NGAL may serve as a sensitive biomarker of early tubular injury, including before overt nephropathy. NGAL may provide complementary, noninvasive tools for detecting and monitoring renal involvement in Fabry disease.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191528","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

Brown Adipocyte BMAL1 Deficiency Is Associated with PVAT Remodeling and Increased Atherosclerosis. 褐色脂肪细胞BMAL1缺乏与PVAT重塑和动脉粥样硬化增加有关。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191791

Ruiyan Xu, Zhenguo Wang, Wenjuan Mu, Juan Zhong, Yao Liu, Yanhong Guo, Jifeng Zhang, Y Eugene Chen, Guohua Li, Lin Chang

{"title":"Brown Adipocyte BMAL1 Deficiency Is Associated with PVAT Remodeling and Increased Atherosclerosis.","authors":"Ruiyan Xu, Zhenguo Wang, Wenjuan Mu, Juan Zhong, Yao Liu, Yanhong Guo, Jifeng Zhang, Y Eugene Chen, Guohua Li, Lin Chang","doi":"10.3390/cells15191791","DOIUrl":"10.3390/cells15191791","url":null,"abstract":"Perivascular adipose tissue (PVAT) is increasingly recognized as an active vascular regulator that influences inflammation, metabolism, and atherosclerotic progression. In healthy vessels, PVAT displays brown adipose-like features and contributes to vascular protection, whereas PVAT dysfunction is associated with adipose whitening, inflammatory activation, and enhanced plaque formation. Circadian clock genes are major regulators of tissue metabolism, yet their role in PVAT biology and atherosclerosis remains incompletely understood. Here, we investigated the function of the core circadian factor BMAL1 in brown adipocytes and PVAT using a brown adipocyte-specific BMAL1 knockout model (Bmal1BAKO) and ApoE-deficient atherosclerosis-prone mice. Transcriptomic profiling of thoracic aortic PVAT and abdominal aortic PVAT revealed that BMAL1 deficiency induces a shift in metabolic gene expression profiles characterized by upregulation of glycolytic and lipogenic gene programs, together with suppression of genes linked to thermogenic and vascular homeostasis. Mechanistically, BMAL1 loss increased Mlxipl (encoding ChREBP) expression, and ChREBP knockdown attenuated the glycolytic-lipogenic transcriptional response to BMAL1 depletion in cultured brown adipocytes. In parallel, BMAL1-deficient PVAT exhibited enlarged lipid droplets, increased oxidative stress-related transcriptional profile, and inflammatory remodeling accompanied by macrophage accumulation. In ApoE-/- mice, brown adipocyte-specific BMAL1 deletion aggravated atherosclerotic lesion formation in both chow-fed aging mice and Western diet-fed young mice, without major changes in systemic energy balance. In conclusion, brown adipocyte BMAL1 deficiency was associated with ChREBP-linked metabolic reprogramming, loss of brown-like PVAT features, oxidative and macrophage-associated remodeling, and increased atherosclerosis.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191299","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

Mesenchymal Stromal Cell Spheroids as an Emerging Regenerative Strategy for Osteonecrosis of the Femoral Head. 间充质间质细胞球体作为股骨头骨坏死的一种新兴再生策略。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191787

Sholpan Mukhlis, Meruyert Imanbekova, Dina Saginova, Madina Sarsenova, Aida Nurgaliyeva, Nursulu Altaeva, Vyacheslav Ogay

{"title":"Mesenchymal Stromal Cell Spheroids as an Emerging Regenerative Strategy for Osteonecrosis of the Femoral Head.","authors":"Sholpan Mukhlis, Meruyert Imanbekova, Dina Saginova, Madina Sarsenova, Aida Nurgaliyeva, Nursulu Altaeva, Vyacheslav Ogay","doi":"10.3390/cells15191787","DOIUrl":"10.3390/cells15191787","url":null,"abstract":"Osteonecrosis of the femoral head (ONFH) is a progressive ischemic bone disorder that may lead to subchondral fracture, femoral-head collapse, and total hip arthroplasty. Impaired regeneration reflects persistent ischemia, endothelial dysfunction, defective angiogenesis and bone remodeling, inflammation, oxidative stress, and dysfunction of endogenous mesenchymal stromal cells (MSCs). Although MSC therapy, particularly with core decompression in precollapse ONFH, is a promising joint-preserving approach, conventional two-dimensional (2D)-expanded MSCs are limited by poor survival and retention, anoikis, disrupted cell-cell and cell-extracellular matrix interactions, and loss of potency during ex vivo expansion. Three-dimensional MSC spheroids may overcome several of these limitations by preserving intercellular and matrix interactions and enhancing resistance to ischemic stress, paracrine signaling, angiogenic activity, immunomodulation, and osteogenic competence. Hypoxia-responsive signaling, autophagy, trophic-factor secretion, and extracellular vesicle-mediated communication may promote angiogenesis-osteogenesis coupling and the restoration of the ischemic bone-vascular niche. This review summarizes the pathophysiological barriers to ONFH regeneration, current evidence and limitations of conventional MSC therapy, biological mechanisms underlying MSC-spheroid activity, and emerging strategies for therapeutic optimization. Importantly, direct evidence demonstrating the superiority of MSC spheroids over conventional MSC preparations specifically in ONFH remains limited. Future translation will require disease-specific comparative studies, standardized GMP-compatible manufacturing, validated potency assays and clinically practical delivery systems.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191582","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 SKP2-Substrate Axis in Hematological Malignancies: Mechanisms of Oncogenesis and Opportunities for Targeted Therapy. 血液恶性肿瘤中的skp2 -底物轴：肿瘤发生机制和靶向治疗的机会。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191796

Yueying Zhang, Omar Faruq, Mariusz Shrestha, Shamila D Alipoor, Hong Chang

{"title":"The SKP2-Substrate Axis in Hematological Malignancies: Mechanisms of Oncogenesis and Opportunities for Targeted Therapy.","authors":"Yueying Zhang, Omar Faruq, Mariusz Shrestha, Shamila D Alipoor, Hong Chang","doi":"10.3390/cells15191796","DOIUrl":"10.3390/cells15191796","url":null,"abstract":"S-phase kinase-associated protein 2 (SKP2), a key substrate-recognition subunit of the Skp1-Cul1-F-box (SCF) E3 ubiquitin ligase complex, promotes the ubiquitin-proteasome-mediated degradation of tumor suppressors such as p27Kip1 and p21(Cip1/Waf1). Through these activities, SKP2 regulates critical cellular processes, including cell cycle progression, apoptosis, metabolic reprogramming, maintenance of cancer stem cell stemness, and contributes to the pathogenesis, therapeutic resistance, and clinical progression of hematological malignancies. Recent advances in protein degradation technologies and regulatory network analysis have highlighted SKP2 and its substrate interactions as promising targets for precision therapies. In this review, we examine the biological functions of SKP2 and regulatory mechanisms governing its substrate spectrum across hematological malignancies, including acute myeloid leukemia, chronic myeloid leukemia, B/NK/T-cell lymphoma, and multiple myeloma. We further review currently available SKP2-targeted therapeutic strategies, including small-molecule inhibitors, molecular glue degraders, and proteolysis-targeting chimeras (PROTACs), and discuss SKP2-related prognostic biomarkers in hematological malignancies. Finally, we outline the key challenges and future directions to guide the development of SKP2-centered therapeutic approaches.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191633","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

Cell Death Induction by MO2455, a Novel Potential Anti-Cancer Agent in Monocytic and T-Cell Leukemia Cells. 一种新的潜在抗癌药物MO2455诱导单核细胞和t细胞白血病细胞死亡。

IF 6 2区生物学

Cells Pub Date : 2026-09-30 DOI: 10.3390/cells15191780

Ankitha Vadi Velu, Kenji Matsuno, Barkha Saraswat, Osamu Ohno, Yu Yingchun, Zhao Zhenkai, Ying Tong, Takahiro Tougan, Taiki Aoshi, Takeji Takamura, Fumiaki Koizumi, Mitsuko Masutani

{"title":"Cell Death Induction by MO2455, a Novel Potential Anti-Cancer Agent in Monocytic and T-Cell Leukemia Cells.","authors":"Ankitha Vadi Velu, Kenji Matsuno, Barkha Saraswat, Osamu Ohno, Yu Yingchun, Zhao Zhenkai, Ying Tong, Takahiro Tougan, Taiki Aoshi, Takeji Takamura, Fumiaki Koizumi, Mitsuko Masutani","doi":"10.3390/cells15191780","DOIUrl":"10.3390/cells15191780","url":null,"abstract":"Despite advances in targeted therapies, treatment resistance and disease recurrence remain major obstacles in leukemia management. Structural modification of clinically successful kinase inhibitors represents a promising approach for discovering novel anti-leukemic agents with improved biological activities. In the present study, we investigated the anti-leukemic activity and mechanism of action of MO2455, a newly synthesized imatinib-derived compound, in monocytic leukemia U937, THP-1, and T-cell leukemia CCRF-CEM cells. MO2455 showed substantial cytotoxic activity against all three cell lines, with IC50 values of 0.83 μM, 0.43 μM, and 0.57 μM in U937, THP-1, and CCRF-CEM cells, respectively. Treatment with MO2455 induced early mitochondrial membrane depolarization, internucleosomal DNA laddering, a significant accumulation of sub-G1 population and increased Annexin V positivity, suggesting typical apoptosis without cell cycle arrest in U937 cells. MO2455 induced γ-H2AX induction and upregulated the pro-apoptotic NOXA and BBC3 genes. THP-1 and CCRF-CEM cells displayed distinct large DNA fragmentation with smearing. In PBMCs from two healthy donors, IC50 values were 0.99 and 0.60 μM, respectively, although the cells remained morphologically healthy without obvious extensive cell death. Overall, MO2455 exhibits substantial anti-leukemic activity and induces cell death through apoptosis and other mechanisms, supporting further investigation as an anti-leukemic agent.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191330","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

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