Melanoma stem cells may contribute to tumor progression not only through intrinsic plasticity, but also by shaping the immune microenvironment. However, their interaction with the monocyte-macrophage compartment remains poorly understood. Melanosphere cultures derived from A375 and WM115 melanoma cell lines were used as an in vitro model enriched for stemness-associated features. THP-1 monocytes were differentiated under a standardized low-dose PMA protocol and exposed to stem cell-conditioned media. Monocyte migration, macrophage transcriptomic and secretory profiling, the effect of macrophage-conditioned medium on NK cytotoxicity and melanoma stem cell phenotype and exploratory clinical relevance in a melanoma patients' cohort were assessed. Both melanosphere cell models were enriched for stemness-associated programs. Stem cell-conditioned media promoted THP-1 monocyte migration, which was reduced by CCR2 inhibition. RNA-seq showed that stem cell-conditioned media induced a shared but non-canonical macrophage phenotype enriched for inflammatory, interferon-related, pro-angiogenic, and immune-regulatory programs. Conditioned media from stem cell-educated macrophages impaired NK-cell cytotoxicity through heat-labile soluble mediators and induced cell line-dependent changes in melanoma stemness-associated transcriptional regulators. In an independent melanoma cohort, a shared stem cell-educated macrophage score was associated with inflammatory macrophage programs and with shorter overall survival. Melanoma stem cells actively shape the monocyte-macrophage compartment by promoting monocyte recruitment and inducing an inflammatory and immunomodulatory macrophage program coupled with downstream effects on NK-cell function and melanoma cell-state regulation. These findings support a bidirectional melanoma stem cell-macrophage axis that warrants validation in more physiological systems.
To determine and compare the effects on differentiation, proliferation, and morphology of dental pulp-derived mesenchymal stem cells (DPSC) and preosteoblasts (pre-OBs) (Saos-2) that are either cocultured or treated with conditioned medium (CM) in vitro. In this experimental in vitro study, DPSC and Saos-2 cells were cocultured either directly-allowing physical contact-or indirectly, using a transwell system. These coculture systems were compared to treatment with CM from these cells over varying time periods. Morphological changes were evaluated using light microscopy, while cell proliferation was assessed with the resazurin colorimetric assay. Osteoblastic differentiation was analyzed by Alizarin Red staining and by quantifying changes in Runt-related transcription factor 2 (RUNX2), osterix (OSX), and osteocalcin (OCN) gene expression via real-time RT-PCR. All experiments were performed in triplicate and data analyzed by Student's t-test, ANOVA, or Mann-Whitney U test. Treatment with CM reduced the cell numbers for both cell types, whereas direct and indirect coculture led to an increase in cell numbers after 8 days of treatment. Morphologically, these treatments induced the formation of more elongated cells with greater cellular extensions compared to control groups. All experimental groups exhibited calcium nodule formation and increased relative expression of RUNX2, OSX, and OCN, consistent with induction of osteogenic differentiation. The results of this study suggest that both direct and indirect coculture of Saos-2 and DPSC cells, as well as treatment with CM, are effective in inducing morphological changes, proliferation, and osteoblastic differentiation. These strategies may therefore serve as useful tools for research into regenerative therapies aimed at repairing bone defects.
This review explores gels that assemble from low-molecular-weight gelator (LMWG) building blocks for use in cell culture, with a focus on fibroblasts and stem cells. These LMWG hydrogels have unique potential for controlling and directing cell growth. We provide an overview of gel tunability and how careful molecular design can direct biological outcomes. The LMWG hydrogel approach to cell growth is based on reversible assembly, potentially enabling cells to be encapsulated and subsequently released. It is possible to easily formulate multiple active ingredients into LMWG hydrogels by co-assembly - a powerful strategy to create multi-functional hybrid hydrogels. Rheological properties can be tuned over orders of magnitude, with stiffness helping control properties like cell invasion or stem cell differentiation. Furthermore, gel dynamics at both molecular and network levels can control factors such as cell adhesion. By developing strategies to shape and pattern these gels, it is possible to create structured assemblies of cells or direct the growth of multi-functional biological tissues. The dynamic characteristics of these gels enables them to evolve, potentially facilitating 4D tissue engineering or the creation of materials that are both bio-instructive and bio-responsive. LMWG hydrogels have been applied both in vitro and in vivo and some are in commercial use. This critical review provides an overview of progress to date, emphasising the unique advantages of the LMWG hydrogel approach, and highlighting concepts that might unlock untapped potential, hence transforming next-generation regenerative medicine.
The therapeutic efficacy of stem cell-based treatments depends critically on maintaining high cell viability through the injection process. Mechanical stress induced on cells during passage through injection needles represents a significant source of cell damage that can compromise therapeutic outcomes. This review examines the current understanding of how needle gauge (diameter) and length affect human stem cell viability, exploring the mechanical forces involved, empirical evidence across different stem cell types, and practical implications for clinical protocols. We analyze the competing demands of minimizing tissue trauma through smaller needles while preserving cell viability and provide evidence-based recommendations for optimizing injection parameters across various clinical applications.
Mismatched allogeneic haematopoietic stem cell transplants (HSCT) are complicated by the presence of pre-existing HLA-specific antibodies targeting the mismatched HLA antigens (DSAs). Data indicates that the presence of DSAs pre-transplant, termed HLA incompatible HSCT, is associated with inferior outcomes and graft failure. Whilst studies acknowledge that DSAs should be avoided there is limited information regarding the impact of specific DSAs and their levels on HSCT outcomes. There is also a recognised lack of knowledge and methods which allow the immunological risk of HLA incompatible HSCT to be defined, with a large volume of data being extrapolated from solid organ transplant data. We have established a stem cell specific flow cytometry crossmatch (SC-FCXM) for the in vitro assessment of the binding capacity of HLA-specific antibodies to CD34+ stem cells. A library of HLA typed expanded human CD34+ progenitor cells from cord blood (CB-CD34+) was generated and used to assess HLA-specific antibody binding of 86 serum samples from the National External Quality Assurance Scheme (NEQAS) Histocompatibility and Immunogenetics crossmatching 2B external proficiency testing scheme issued between 2023 and 2025. Sera were analysed using LABScreen Single Antigen (LSSAg) Class I and II and donor specific HLA antibodies (DSAs) were identified for each CB-CD34+ and serum combination. A range of DSAs targeting single HLA antigens, plus multiple HLA-specific Class I, Class II or a combination of Class I and II antibodies based on mean fluorescence intensity (MFI) was examined. The impact of increasing DSA MFI on SC-FCXM reactivity was determined by correlation and regression studies comparing cumulative peak LSSAg MFI versus median fluorescence intensity of anti-human IgG APC as determined by the SC-FCXM (APC Median SC-FCXM). As LSSAg MFI of DSAs targeting HLA-A (p = 0.0001), -B (p = 0.0001) and -DRB1 (p = 0.0155) increased, there was significant correlation with APC Median SC-FCXM, but no correlation (p > 0.05) between LSSAg MFI and APC Median SC-FCXM for HLA-C, -DQB1, -DQA1 or -DPB1. A significant correlation (p ≤ 0.05) was observed for multiple HLA Class I (p = 0.0005), Class II (p = 0.0001), plus combinations of Class I and II DSAs (p = 0.0013) between combined LSSAg MFI and APC Median SC-FCXM. The extrapolation of this preliminary data has provided an indication of which DSAs and their levels (as determined by LSSAg MFI) cause FCXM reactivity against CD34+ stem cells, which could prove to be relevant in HLA incompatible HSCT. However, the assay currently remains a proof-of-concept and further work is required to establish clinical correlation of the results to patient outcomes.
The lifespan of annual plants is strictly controlled by the senescence of stem cells and the cessation of the inflorescence meristem (IM). A "senescence factor" has long been proposed from developing fruit to trigger proliferative arrest in the IM. Here, we show that jasmonic acid (JA) accumulates in the IM with aging and directly represses WUSCHEL expression and cytokinin accumulation by the key transcription factor MYC2. We demonstrate that sucrose originating from siliques triggers local JA biosynthesis in the IM and causes the senescence of stem cells and arrest of meristematic proliferation. Moreover, the expression of the sugar efflux transporter SWEETs is increased in the IM at the late development stage and is directly activated by MYC2. The mobile sucrose and local JA signaling forms a positive feedback loop to trigger stem cell repression in the IM. Our results suggest that sucrose from siliques acts as a senescence factor and together with the previously described auxin and FRUITFULL/miR172 routes, defines the timing of IM aging, which has great economic and fitness importance for plants.
Aberrant activation of HIF‑1α contributes to the maintenance of CSC phenotypes in various malignancies. Our previous work revealed that ANXA3 is up‑regulated in OS cells. Here, we further investigated how ANXA3 regulates CSC‑like properties of OS cells through the HIF‑1α/VEGF signaling pathway. Lentiviral vectors were used to modulate ANXA3 expression in OS cell lines. The expression of stemness‑associated genes was examined by qPCR and Western blotting, and sphere‑formation assays were performed to evaluate CSC self‑renewal capacity. Migration, invasion, and clonogenic survival under cisplatin treatment were assessed using Transwell and colony‑formation assays. An orthotopic intratibial implantation model in NOD-SCID mice was established to evaluate the effects of ANXA3 on tumor growth, metastasis, and CSC‑related features. Potential signaling mechanisms were analyzed by Western blotting and ELISA, and pathway‑specific inhibitors were applied to dissect the PI3K/Akt/mTOR-HIF‑1α/VEGF cascade. ANXA3 expression was markedly elevated in osteosarcoma spheres compared with parental cells. ANXA3 knockdown down‑regulated stemness‑related genes, impaired sphere formation, and increased cisplatin sensitivity, whereas ANXA3 overexpression produced opposite effects. In vivo, ANXA3 silencing significantly suppressed tumor growth and pulmonary metastasis. Mechanistically, ANXA3 activated the PI3K/Akt/mTOR pathway, thereby enhancing HIF‑1α/VEGF expression. Knockdown of PI3K or HIF‑1α abrogated ANXA3‑induced stemness and chemoresistance, confirming the signaling axis mediates ANXA3‑driven oncogenic effects. ANXA3 plays a critical role in maintaining CSC‑like traits in osteosarcoma by up‑regulating the HIF‑1α/VEGF pathway in a PI3K/Akt/mTOR‑dependent manner. Targeting ANXA3 or its downstream signaling components may represent a promising therapeutic strategy for reversing CSC phenotypes and overcoming chemoresistance in osteosarcoma.
ERCC6L2 disease (ED) is a rare bone marrow failure syndrome caused by biallelic germline mutations in ERCC6L2. ED leads to the accumulation of somatic TP53 mutations, myelodysplastic syndrome, and acute myeloid leukemia (AML) with erythroid predominance and poor prognosis. While ERCC6L2 is implicated in DNA replication and repair, the transcriptomic events underlying delayed erythropoiesis and leukemic progression remain largely undefined. To delineate these processes, we leverage bulk and single-cell transcriptomics of patient fibroblasts, bone marrow, and peripheral blood across disease stages, including single-cell TP53 genotyping. We identify disease-associated erythroid dysregulation and ferroptotic stress emerging prior to TP53 mutation, highlighting an early vulnerability in ED leukemogenesis. We compare ED to Shwachman-Diamond syndrome (SDS) to reveal shared and disease-specific transcriptional programs. TP53 mutations in ED and SDS arise in hematopoietic stem and progenitor cells but do not independently drive changes in cell cycle or stress pathways during erythropoiesis, despite harboring distinct germline defects. Both diseases converge in late erythropoiesis into a stress state characterized by ferroptotic signaling, G1 arrest, and BCL2L1 upregulation. As a disease-specific pattern, ED shows aberrant erythroid priming with TP53-driven differentiation arrest shaping progression toward erythroid leukemia. Thereby, we establish the first patient-level single-cell map of ED and provide a curated resource for future work on ED, SDS, and TP53-driven leukemogenesis. Overall, our findings in pre-malignant ED offer a window into early alterations leading to high-risk leukemia.
Traumatic brain injury (TBI) is a leading cause of persistent cognitive, motor, and neuropsychiatric impairment, arising from both the initial mechanical insult and a prolonged cascade of secondary injury processes. While primary injury reflects structural damage, secondary mechanisms, including neuroinflammation, oxidative stress, apoptosis, and blood-brain barrier disruption, evolve over time and critically influence long-term outcomes. Despite extensive investigation, therapies targeting isolated components of secondary injury have demonstrated limited clinical success, highlighting the need for approaches that support coordinated neural repair. Stem cell-based therapies have emerged as a promising neurorestorative strategy. Rather than replacing lost neurons directly, transplanted cells primarily act through paracrine signaling, immunomodulation, neurotrophic support, and preservation of vulnerable neural networks. However, clinical translation has been constrained by heterogeneity in cell sources, delivery routes, treatment timing, and outcome measures, limiting mechanistic interpretability across trials. This review presents a mechanism-aligned translational framework linking injury stage, biological targets, route of administration, and clinically meaningful outcomes across stages of TBI. We integrate current knowledge of post-injury repair mechanisms with evidence from recent human clinical trials of stem cell therapies. Particular emphasis is placed on safety, feasibility, and emerging signals across structural and functional endpoints, as well as how injury stage, biological targets, delivery strategies, and meaningful endpoints interact to shape treatment responsiveness and inform biomarker-guided clinical trial design.
A dysregulated inflammatory response to infection can lead to sepsis, a leading cause of mortality worldwide, and effective anti-inflammatory therapies remain limited. Mesenchymal stem/stromal cells (MSCs) are attractive candidates as immunomodulatory agents. This study evaluated whether genetic modification of MSCs to express interleukin-10 (IL-10), a key anti-inflammatory cytokine, enhances their immunomodulatory effects. Bone marrow-derived MSCs from C57Bl/6 mice were genetically engineered by lentiviral transduction to express mouse IL-10 (MSC-IL-10). The immunomodulatory activity in vitro was assessed by co-cultures with macrophages stimulated with LPS and IFN-γ, as well as in Con A-stimulated splenocytes. BALB/c mice subjected to lipopolysaccharide (LPS)-induced endotoxemia were treated with vehicle, dexamethasone, wild-type MSCs (MSC-WT), or MSC-IL-10. Survival, plasma cytokines, leukocyte profiles, CD11b⁺ inflammatory cells, and organ histopathology and biodistribution were evaluated in vivo. MSC-IL-10 maintained the mesenchymal phenotype and multipotent characteristics while exhibiting robust IL-10 expression. In in vitro assays, MSC-IL-10 significantly decreased the production of the cytokines TNF-α, IL-1β, IL-6, IL-12 or Nos2 expression by stimulated macrophages or splenocytes, demonstrating superior immunomodulatory effects compared to MSC-WT. In in vivo mice models, MSC-IL-10 significantly reduced systemic pro-inflammatory cytokines, restored circulating leukocyte counts, and attenuated CD11b⁺ (Mac-1 integrin) inflammatory cell recruitment, surpassing MSC-WT-treated groups. Importantly, MSC-IL-10 mitigated tissue damage mainly to lungs and exhibited biodistribution to liver, lungs and spleen in LPS-challenged mice. These results support an enhanced immunomodulatory effect of IL-10-expressing MSCs as a promising cell-based therapeutic approach for sepsis and other inflammatory and immune mediated disorders.
This study aims to identify potential biomarkers for diabetic retinopathy (DR) by focusing on genes associated with mesenchymal stem cell-derived exosomes (MSCs-Exo). By integrating DR transcriptome data with the protein dataset of MSCs-Exo, we utilized a comprehensive array of bioinformatics techniques, including weighted gene coexpression network analysis, Mfuzz clustering, and machine learning algorithms such as least absolute shrinkage and selection operator regression and random forest to pinpoint key genes. Functional mechanisms were explored through functional enrichment analysis, immune infiltration, and single-cell RNA sequencing. The immunohistochemistry and Western blotting were used for validation on DR mice models. Our comprehensive analysis identified 16 hub genes associated with MSCs-Exo. Through the application of interpretable machine learning techniques, YBX1 and PSMA7 were further identified as central genes within this network. A predictive diagnostic model for DR was developed and validated using receiver operating characteristic curve analysis, which demonstrated modest diagnostic efficacy, as indicated by an area under the curve exceeding 0.7. Importantly, experimental validation showed that the protein expression levels of YBX1 and PSMA7 were significantly reduced in the retinal tissues of DR mice compared with the control group (P < 0.05). Functional enrichment analysis suggested that YBX1 and PSMA7 are involved in critical biological processes, specifically the regulation of protein and amino acid metabolism. In addition, immune infiltration results show that they are significantly associated with the immune dysregulation of DR, especially in CD4T memory cells. Single-cell analysis also supported the above finding. These findings suggest that YBX1 and PSMA7, derived from MSCs-Exo, may serve as potential biomarkers for DR. Further studies are needed to confirm their clinical utility and therapeutic relevance.
Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only potentially curative treatment. We report a single-centre series of three consecutive SS patients treated with mogamulizumab as bridging therapy to allo-HSCT using thiotepa-based reduced-intensity conditioning. Mogamulizumab induced rapid clearance of circulating Sézary cells and significant clinical improvement. All patients achieved early and stable full donor chimerism and complete remission. Post-transplant GVHD occurred but was manageable with standard therapy. Early use of mogamulizumab may provide effective disease control and facilitate successful allo-HSCT in SS. The authors have confirmed clinical trial registration is not needed for this submission.
Huntington's disease (HD) and ankylosing spondylitis (AS) are genetically and pathophysiologically distinct conditions, and their concurrent management may present a complex clinical challenge. A case is reported of a 35-year-old man with genetically confirmed HD and concurrently diagnosed AS, treated with autologous mesenchymal stem cell (MSC) therapy over three consecutive monthly sessions (50 million MSCs per session, total 150 million administered, intravenous and epidural routes). Validated disease-specific assessments were performed at each visit by the treating neurologist before the cell administration of that day: the Unified Huntington's Disease Rating Scale motor score (UHDRS motor), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Three serial assessments captured changes from baseline (cumulative dose 0) through cumulative doses of 50 million and 100 million MSCs, after which the third (final) dose was administered without subsequent reassessment. Over the two-month observation period, UHDRS motor score declined from 19 to 2, BASFI from 4.0 to 1.0 (with a transient increase to 8.5 at the second visit), and BASDAI from 2.0 to 1.0. No serious short-term adverse events were observed during the active treatment period. Given the single-patient design, concurrent pharmacotherapy, unblinded assessment, absence of objective biomarkers, and absence of post-third-dose assessment, causal attribution to MSC therapy cannot be established. The observation is presented as hypothesis-generating and warrants further investigation under controlled conditions.
BackgroundWith the emergence of haploidentical transplantation, children with sickle cell disease (SCD) are increasingly pursuing hematopoietic stem cell transplantation (HSCT) as a curative treatment approach. However, suboptimal medication adherence remains a persistent challenge in both SCD and HSCT populations. Adherence to complex medication regimens is crucial to reducing the risk of severe complications and early mortality, yet no synthesis has evaluated patterns of adherence among patients with SCD post-HSCT.MethodWe conducted an integrative review, searching PubMed, CINAHL, and PsycINFO from April 2025 to May 2025 for studies measuring medication adherence in children (≤21 years) with SCD and/or HSCT. Studies were included if they reported adherence rates and excluded if they involved adherence interventions or drug development trials.ResultsEighteen studies met inclusion criteria: 12 addressed SCD and 6 focused on HSCT. No studies specifically examined adherence in patients with SCD post-HSCT. Adherence rates to disease-modifying medications in SCD ranged from 10% to 89%, while post-HSCT adherence ranged from 40% to 73%. Nonadherence was associated with increased complications across both populations.DiscussionThese findings highlight a critical research gap and provide a foundation for targeted adherence interventions. Addressing this gap is essential to advance nursing practice, improve adherence, and optimize clinical outcomes in pediatric hematology and HSCT care.
Meat production and ethical concerns related to animal welfare have led to an increase in research into the creation of conventional meat. These technologies rely on the isolation, multiplication, and controlled differentiation of animal cells, which can potentially reduce negative environmental impact while maintaining comparable nutritional and sensory properties. The aim of this study is to comprehensively analyze and compare selected cell types used in the production of cultured meat, such as fibroblasts, satellite cells, adipocytes, and pluripotent cells: embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). It is important to consider the proliferative capacity, differentiation potential, suitability in scalable bioprocessing systems, and their impact on the structure and sensory properties of muscle tissue. This analysis demonstrates that no single cell type can fully replicate the complex structure of native muscle tissue. Satellite cells are responsible for the formation of muscle fibers, fibroblasts provide support through the synthesis of the extracellular matrix, and adipocytes contribute to the flavor and juiciness of the final product. Pluripotent cells differentiate into all of cell lineages, but their use is associated with regulatory and ethical considerations. This work also addresses key aspects of bioprocess engineering, such as scalability, culture conditions, and the importance of 3D cell culture and cell co-cultures in restoring tissue structure. Furthermore, regulatory, ethical, and economic issues affecting the feasibility of implementing the technology for industrial production are considered. In summary, the data presented indicate that the development of cultured meat requires an integrated approach combining appropriate cell selection, process optimization, and compliance with regulatory and ethical requirements.
Endoplasmic reticulum (ER) stress is central to the onset and progression of metabolic and inflammatory disorders, such as insulin resistance, hepatic steatosis, and cardiovascular dysfunction. The unfolded protein response, triggered by ER stress, induces maladaptive pathways through PERK, IRE1, and ATF6, leading to inflammation, apoptosis, and cellular dysfunction. Targeted ER stress modulation is an attractive therapeutic approach, and recent developments in bioengineering have enabled precise delivery of modulatory agents using cell-penetrating peptides and adipose-derived stem cells. On the one hand, cell-penetrating peptides (CPPs) enable intracellular delivery of therapeutic cargoes such as siRNA, peptides, or small-molecule targeting key ER stress mediators, including CHOP, GRP78, IRE1, and NF-κB. CPP-mediated delivery systems restore ER homeostasis, reduce inflammatory signaling, and improve cellular survival in hepatocytes, pancreatic β-cells, and cardiomyocytes. Simultaneously, adipose tissue-derived stem cells (ADSCs), which are derived from lipo-aspirated fat tissue, induce paracrine effects through the secretion of anti-inflammatory cytokines (i.e., IL-10), growth factors (i.e., VEGF, HGF, TGF-β), and antioxidants that regulate ER stress responses. ADSCs also have adipogenic and endothelial differentiation, playing roles in repairing tissue and metabolic homeostasis. Downregulation of ER stress markers and mitigation of oxidative stress increase their therapeutic efficacy for metabolic disorders. Collectively, this bioengineered synergy of CPPs and ADSCs represents a multifunctional therapeutic platform to target ER stress and its downstream effects. This synergistic approach has translational potential for precision medicine in metabolic pathophysiology, advancing from laboratory innovations to clinical applications.
In the context of sexual reproduction, primordial germ cells (PGCs) are the progenitors of life; they develop into gametes and safeguard fertility. By virtue of their diverse reproductive strategies, fishes provide appealing models to study germ cell formation and functional gonadogenesis. This review aims to consolidate our understanding of PGC development in teleosts by evaluating the developmental milestones of germ cell formation in contrast with other model animals. Here, we revisit germ plasm assembly in gametes, re-examining the extent and nature of parental contributions to germ cell inheritance. We further examine how germ cell fate in teleosts is governed by germ plasm inheritance, whereby lineage identity arises through selective retention and stabilisation of maternal determinants rather than de novo specification. Following this, we demonstrate that a coordinated network of molecular pathways and effector genes drives PGC signalling, mobilization, and homing to the gonadal niche. Then, we highlight that, in contrast to mammals, teleost germ cell specification is largely uncoupled from genome-wide epigenetic reprogramming and instead relies on maternally inherited messages and post-transcriptional regulation to establish germline identity. Finally, we explore the interplay between newly harboured germ cells and gonadal somatic cells that underpins sexual identity acquisition. Collectively, these findings establish a conceptual framework in which germ plasm inheritance, post-transcriptional regulation, and soma-germline interactions jointly govern germ cell fate, sexual identity, and functional fertility in teleosts.
Therapy-Induced Senescence (TIS) is increasingly recognized as a clinically relevant outcome of anticancer therapy, particularly after sublethal genotoxic stress. In Non-Hodgkin Lymphomas (NHL), TIS may coexist with apoptosis and contribute to treatment heterogeneity by enabling the long-term survival of dam-aged but viable tumor cells. The aim of this article is to synthesize the core molecular mechanisms of TIS in NHL, and to highlight druggable senolytic and senomorphic strate gies that may improve disease control and reduce the risk of relapse. A narrative review was conducted using mechanistic and translational literature addressing DNA Damage Response (DDR) signaling, p53-p21 and p16^INK4a^-RB checkpoint pathways, Senescence-Associated Secretory Phenotype (SASP), epigenetic remodeling, senescence escape, stemness acquisition, and therapeutic targeting of senescent tumor cells. Searches were performed in PubMed / MEDLINE, Scopus, and Google Scholar using combinations of the terms "therapy-induced senescence", "cellular senescence", "SASP", "senolytic", "senomorphic", and "senescence escape". Priority was given to studies published between 2010 and 2026, while older land-mark studies were included when mechanistically essential. TIS is initiated by persistent DDR signaling (ATM/ATR→CHK1/CHK2) with downstream activation of p53-p21 and/or p16^INK4a^-RB pathways, resulting in stable growth arrest. Senescent lymphoma cells may acquire a SASP that remodels the tumor microenvironment and modulates immune responses. Epigenetic reprogramming (e.g., SAHF formation, H3K9me3 dynamics, lamin B1 loss) supports phenotypic plasticity and may enable escape from senescence with stem-like features, contributing to residual dis-ease persistence and relapse biology. Therapeutically, senolytic approaches (e.g., BH3 mimetics, BCL-2/BCL-xL antagonists) and senomorphic strategies (targeting SASP regulators such as NF-κB, JAK/STAT, and mTOR) represent potentially actionable therapeutic approaches. Emerging senolytic Chimeric Antigen Receptor T-cell (CAR-T cell) strategies targeting senescence-associated surface programs, such as uPAR, further expand the therapeutic landscape, although these approaches remain at a preclinical stage at the time of writing this review. In lymphomas, TIS is a dynamic stress-adaptation state that can support persistence and relapse. Rational integration of senescence biomarkers, timing-based therapies, and targeted senolytic/senomorphic interventions may enhance long-term treatment efficacy; however, most senescence-targeted strategies remain investigational and require lymphoma-specific clinical validation.
Glioma stem cells (GSCs) are pivotal drivers of tumor progression and therapeutic resistance; however, the underlying regulatory mechanisms have not been fully elucidated. This study aimed to identify novel oncogenic drivers in glioma via a comprehensive multiomics analysis. We integrated three datasets to screen potential oncogenic drivers. Functional experiments were performed to examine the effects of C1orf226 on glioma cell proliferation, cell cycle, epithelial-mesenchymal transition (EMT), and apoptosis. Additionally, tumor sphere formation assays, ALDH+/CD133+ cell detection, and stemness marker analysis were used to evaluate the role of C1orf226 in GSC stemness. Mechanistic studies involving immunoprecipitation (IP) and ubiquitination assays were applied to characterize the interaction between C1orf226 and PLK1, as well as their regulation on β-catenin stability and Wnt/β-catenin signaling. Rescue assays further verified the functional crosstalk between C1orf226 and PLK1. Xenograft mouse models were used in vivo to assess the impacts of C1orf226 knockdown on tumor growth and stemness markers. C1orf226 was significantly upregulated in glioma tissues compared with normal brain tissues. Its high expression correlated with shorter patient survival and served as an independent prognostic factor in the CGGA cohort. In vitro, C1orf226 exerted oncogenic function by facilitating cell proliferation, cell cycle progression, EMT-like processes, and stemness, and suppressing apoptosis. Mechanistically, C1orf226 interacts with PLK1 to block its degradation, thereby activating PLK1 and downstream Wnt/β-catenin signaling. Rescue experiments verified that PLK1 overexpression restored β-catenin stability, Wnt/β-catenin target gene expression, and GSC properties impaired by C1orf226 knockdown. In vivo, C1orf226 knockdown restrained xenograft growth and reduced stemness marker levels, and PLK1 co-expression abrogated these effects. Our findings reveal that C1orf226 is a PLK1-dependent regulator of Wnt/β-catenin signaling and GSC plasticity, highlighting its potential as a promising therapeutic target in glioma.
Being a staple crop and growing over larger area, rice (Oryza sativa L.) generates a vast quantity of straw as a by-product. However, high fibre and silica content present in rice straw makes it difficult to utilize as a quality livestock feed or for industrial utilization, thus necessitating to identify genetic resources with lower silica content and enhanced straw digestibility. In this study, 207 diverse rice germplasm accessions belonging to 2 K rice diversity panel and 25 cultivated varieties were evaluated for straw cell wall components (silica, lignin and cellulose), agronomic traits (plant height, number of tillers, stem thickness) and in-vitro digestibility (acid detergent fibre). Wide variation was observed for silica (4.3-15.7%), lignin (4.9-29.5%), cellulose (20.3-45.2%), plant height (65.6-197.0 cm), number of tillers (4.0-19.0), stem thickness (0.9-9.2 mm) acid detergent fibre (ADF; 45.1-73.0%). Correlation analysis revealed a strong negative relationship between silica and organic as well as dry matter digestibility while lignin displayed variable effects depending on its interaction with other components. Multi-locus-Genome-wide Association Studies (ML-GWAS) with a subset of 154 rice accessions using 208,846 SNPs identified 33 significant marker-trait associations (MTAs) across genome for straw silica, lignin, cellulose, and ADF content. Major MTAs co-localized with known genes involved in silicon uptake (OsOPT2, OsOPT3, OsUCP2), lignin biosynthesis (4CL3, WRKY71, OsACS7), and cellulose synthesis (WAK12, BGLU4, OsMPS). Haplotype analyses of key candidate genes revealed superior alleles associated with up to 15.9% lower silica and 26.9% lower lignin content, with corresponding higher expression in relevant tissues. Selected rice accessions with favourable alleles and balanced ADF, lignin, and silica showed improved in-vitro digestibility, providing promising genetic resources for enhancing rice straw palatability. These findings offer valuable insights into the genetic basis of straw quality traits and identify potential donors for breeding programs aimed at developing rice varieties with improved straw value for sustainable agriculture and bioenergy use.