bims-mithem 2025-09-28 papers

Issue of 2025–09–28
five papers selected by
Tim van Tienhoven, Erasmus Medical Center

Leuk Res. 2025 Sep 13. pii: S0145-2126(25)00589-2. [Epub ahead of print]158 108099

Pathogenic mechanisms and targeted therapies for anemia in myelodysplastic syndromes.

Doudou Chang, Linhua Yang, Ruijuan Zhang.

Myelodysplastic Syndromes (MDS) are malignant neoplasms of the myeloid lineage originating from hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis, blood cell dysplasia, and a high risk of transformation to acute leukemia. Anemia affects up to 90 % of MDS patients, significantly increasing symptom burden, impacting quality of life, accelerating disease progression, and is associated with increased morbidity and mortality. The limited therapeutic landscape for addressing anemia in MDS presents a significant challenge in clinical management. This review explores the mechanisms of anemia in MDS（including low-risk MDS and high-risk MDS）, covering disturbances in hematopoiesis, telomere dynamics, inflammation, immune dysregulation, alterations in iron metabolism, and the role of the bone marrow microenvironment. We examine how these factors contribute to the complex pathophysiology of MDS-related anemia and discuss their implications for treatment strategies. Furthermore, we highlight recent advances in understanding the molecular basis of MDS, which have paved the way for novel therapeutic approaches. These include targeted therapies addressing specific genetic mutations, immunomodulatory agents, and innovative approaches to stimulate effective erythropoiesis. We also review emerging treatments such as Luspatercept, along with other novel agents targeting specific pathways, and ongoing clinical trials exploring combination therapies and personalized treatment strategies.

Keywords: Anemia; Bone marrow microenvironment; Epigenetics; Erythropoiesis; Genetic mutations; Immune dysregulation; Inflammation; Myelodysplastic syndromes

DOI: https://doi.org/10.1016/j.leukres.2025.108099

Int J Mol Sci. 2025 Sep 15. pii: 8968. [Epub ahead of print]26(18):

The Impacts of Dengue Virus Infection on Mitochondrial Functions and Dynamics.

Showkot Ahmed, Réka Dorottya Varga, Jinsung Yang.

Dengue virus (DENV) is a mosquito-borne flavivirus responsible for a significant global disease burden, especially in tropical and subtropical regions. DENV critically manipulates host cell mitochondria to ensure its replication and survival. The clinical manifestations are well-studied and how dengue infection significantly alters the mitochondrial dynamics, and the subsequent functional cellular homeostasis has been unveiled. This review discusses the strategies by which DENV alters mitochondrial functions and dynamics. It particularly focuses on the virus-induced suppression of mitochondrial quality control mechanisms like mitophagy. Moreover, the dichotomous role of mitophagy in supporting DENV replication is highlighted. By incorporating recent studies about DENV-host interactions at the mitochondrial interface, mitochondria, as regulators and targets in dengue pathogenesis, are suggested as possible molecular targets for therapeutic intervention.

Keywords: biogenesis; cellular homeostasis; dengue virus; mitochondria; mitochondrial bioenergetics; mitochondrial dynamics; mitophagy

DOI: https://doi.org/10.3390/ijms26188968

J Transl Med. 2025 Sep 24. 23(1): 1005

Mitochondria-driven inflammation: a new frontier in ovarian ageing.

Wenhan Ju, Binghan Yan, Danping Li, Fang Lian, Shan Xiang.

Ovarian ageing is a key factor in the decline of female fertility. It is primarily characterised by diminished oocyte quality, follicular depletion, and dysregulated hormone levels. In recent years, mitochondria-driven inflammation has emerged as a potential mechanism in ovarian ageing. Mitochondrial dysfunction results in the accumulation of reactive oxygen species (ROS) and the release of mitochondrial DNA (mtDNA), as well as the leakage of mitochondrial components and metabolites into the cytosol or extracellular space. These elements act as damage-associated molecular patterns (DAMPs), activating inflammasomes like NLRP3, thereby initiating and amplifying innate immune responses and contributing to sustained inflammation. Furthermore, an imbalance in mitochondrial quality control mechanisms can worsen the spread and persistence of inflammatory responses. In this study, we present a comprehensive overview of the signalling origins, molecular mechanisms of amplification, and key regulatory nodes involved in mitochondria-driven inflammation during ovarian ageing. Finally, we summarise potential therapeutic strategies targeting mitochondria-driven inflammation, offering novel perspectives and targets for delaying ovarian ageing and enhancing female reproductive health.

Keywords: Damage-associated molecular patterns; Inflammation; Mitochondria; Mitochondrial dysfunction; Ovarian ageing

DOI: https://doi.org/10.1186/s12967-025-06966-6

Biochem Pharmacol. 2025 Sep 23. pii: S0006-2952(25)00624-0. [Epub ahead of print]242(Pt 3): 117359

Pursuing healthy aging and longevity through natural product and stem cell-driven rejuvenation.

Di Wu, Qinzheng Xu, Shuang Wu, Jiachen Tan, Faheem Ahmed Khan, Nuruliarizki Shinta Pandupuspitasari, Chunjie Huang.

Aging is an inevitable biological process associated with progressive physiological decline and increased disease susceptibility. Cellular senescence stands as a key mechanism among the hallmarks of aging, which is characterized by irreversible cell-cycle arrest, chromatin remodeling, and a pro-inflammatory senescence-associated secretory phenotype (SASP). Importantly, SASP drives inflammaging and propagates senescence via a bystander effect, exacerbating tissue dysfunction. Recent advances in senolytic therapies and senostatics offer promising strategies to eliminate or rejuvenate senescent cells, improving physiological function in aged and disease models. Notably, panobinostat has emerged as an effective post-chemotherapy senolytic, mitigating chemoresistance. However, current senolytics face challenges, including off-target effects and limited clinical applicability. Growing evidence highlights natural products (e.g., polyphenols, flavonoids) and stem cell therapies as potential anti-aging interventions, with demonstrated efficacy in age-related disease models and ovarian rejuvenation. Despite progress, key hurdles remain in developing personalized, multi-target therapies that safely modulate aging trajectories. This review explores the mechanisms of cellular senescence, anti-aging mechanisms of phytochemicals, and phytochemicals and stem cell-therapy in ovary rejuvenation. We further discuss the challenges in developing "tailor-made" anti-aging interventions that rewire the aging trajectory, which will be critical for achieving healthy aging.

Keywords: Anti-aging intervention; Cellular senescence; Chemoresistance; Natural product; Stem cell therapy

DOI: https://doi.org/10.1016/j.bcp.2025.117359

Blood. 2025 Sep 22. pii: blood.2024028195. [Epub ahead of print]

Clonal tracing of blood stem cells across mouse and human lifespans.

Alejo E Rodriguez-Fraticelli.

For over sixty years, blood researchers have been counting clones with every tool at their disposal. Inspired by phage and fly geneticists, Till and McCulloch irradiated mice to induce chromosomal aberrations. Using this labeling strategy, they demonstrated that different types of blood cells shared the same mutation in every spleen colony, thereby proving the existence of hematopoietic stem cells. Since their breakthrough, technological advances have enabled researchers to quantify hematopoiesis at single-cell resolution in increasingly complex samples across both mice and humans. With these modern sophisticated lineage tracing methods, our foundational understanding of the blood system is being reshaped. For instance, we now interpret hematopoietic architecture as arising from stem and progenitor cells of diverse developmental origins, each with distinct fate biases encoded by unique regulatory states. Interacting with this regulatory layer, genetic mutations and epimutations arise, expanding clonally and becoming pervasive with age. Together, clonal heterogeneity and age-driven clonal selection may underlie the perplexing diversity of therapy responses in cancer and beyond. As these paradigm-shifting insights gain traction, clonal tracing is being adopted across dozens of biological and clinical studies. Here, we review the modern toolbox of clonal tracking technologies, with a focus on next-generation sequencing-based approaches, and provide a practical guide for matching specific research questions with optimal experimental strategies.

DOI: https://doi.org/10.1182/blood.2024028195