TMEM158, as plasma cfRNA marker, promotes proliferation and doxorubicin resistance in ovarian cancer
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Emerging roles of exosomes in diagnosis, prognosis, and therapeutic potential in ovarian cancer: a comprehensive review
Ovarian cancer is a leading cause of cancer-related deaths in women, and the development of chemoresistance remains a major challenge during and after its treatment. Exosomes, small extracellular vesicles involved in intercellular communication, have emerged as potential biomarkers and therapeutic targets in ovarian cancer. This review summarizes the current literature on differences in exosomal protein/gene expression between chemosensitive and chemoresistant ovarian cancer, and the effects of exosomal modifications on chemotherapeutic response. Clinical studies have identified alterations in several exosomal components from ovarian cancer tissues and serum samples arising as a consequence of chemosensitivity, which indicates their potential usefulness as potential biomarkers for predicting the development of chemoresistance. Interventional investigations from in vitro and in vivo studies demonstrated that modulation of specific exosomal components can influence ovarian cancer cell phenotypes and individual responses to chemotherapy. Exosomal delivery of chemotherapeutic agents, such as cisplatin, has presented as a potential targeted drug delivery strategy for overcoming chemoresistance in preclinical models. In summary, this review highlights the potential for exosomal proteins and genes to be useful biomarkers for predicting chemotherapy response and being therapeutic targets for overcoming chemoresistance in ovarian cancer. However, future research is still needed to validate these findings and explore the clinical utility of exosomal biomarkers and therapeutics in ovarian cancer management. In addition, understanding the molecular mechanisms underlying exosome-mediated chemoresistance may provide valuable insights for the development of personalized therapeutic strategies, improving outcomes for patients with ovarian cancer.
piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer
Conventional targeted therapies primarily rely on small molecules and proteins. However, they often struggle to enter specific protein conformations, which limits their therapeutic effectiveness. In contrast, RNA therapy is emerging as a more precise and effective targeting strategy. Through differential analysis comparing Pandora-Seq data with clinical samples, we discovered that the small RNA piR-28846 naturally, occurring in human body, exhibited low expression levels in ovarian cancer tissues. Experimental results indicate that piR-28846 inhibits the growth of ovarian cancer cells. Additionally, piR-28846 demonstrated significant therapeutic effects in xenograft models and ovarian cancer-like organoids. Further studies revealed that piR-28846 binds to NSUN2 and down-regulates it, which in turn affects the stability of KPNA2 mRNA. Notably, KPNA2 negatively regulates NSUN2 expression and localization. Given its inhibitory effects observed in vivo, in vitro, and in the ovarian cancer organoid model, we believe piR-28846 has strong potential as a small nucleic acid therapy of ovarian cancer.
Energy metabolism in health and diseases
Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, extensive metabolic reprogramming occurs, resulting in impaired glucose metabolism and mitochondrial dysfunction, which accelerate disease progression. Recent investigations into key regulatory pathways, including mechanistic target of rapamycin, sirtuins, and adenosine monophosphate-activated protein kinase, have considerably deepened our understanding of metabolic dysregulation and opened new avenues for therapeutic innovation. Emerging technologies, such as fluorescent probes, nano-biomaterials, and metabolomic analyses, promise substantial improvements in diagnostic precision. This review critically examines recent advancements and ongoing challenges in metabolism research, emphasizing its potential for precision diagnostics and personalized therapeutic interventions. Future studies should prioritize unraveling the regulatory mechanisms of energy metabolism and the dynamics of intercellular energy interactions. Integrating cutting-edge gene-editing technologies and multi-omics approaches, the development of multi-target pharmaceuticals in synergy with existing therapies such as immunotherapy and dietary interventions could enhance therapeutic efficacy. Personalized metabolic analysis is indispensable for crafting tailored treatment protocols, ultimately providing more accurate medical solutions for patients. This review aims to deepen the understanding and improve the application of energy metabolism to drive innovative diagnostic and therapeutic strategies.
Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys
The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.
Breast cancer: pathogenesis and treatments
Breast cancer, characterized by unique epidemiological patterns and significant heterogeneity, remains one of the leading causes of malignancy-related deaths in women. The increasingly nuanced molecular subtypes of breast cancer have enhanced the comprehension and precision treatment of this disease. The mechanisms of tumorigenesis and progression of breast cancer have been central to scientific research, with investigations spanning various perspectives such as tumor stemness, intra-tumoral microbiota, and circadian rhythms. Technological advancements, particularly those integrated with artificial intelligence, have significantly improved the accuracy of breast cancer detection and diagnosis. The emergence of novel therapeutic concepts and drugs represents a paradigm shift towards personalized medicine. Evidence suggests that optimal diagnosis and treatment models tailored to individual patient risk and expected subtypes are crucial, supporting the era of precision oncology for breast cancer. Despite the rapid advancements in oncology and the increasing emphasis on the clinical precision treatment of breast cancer, a comprehensive update and summary of the panoramic knowledge related to this disease are needed. In this review, we provide a thorough overview of the global status of breast cancer, including its epidemiology, risk factors, pathophysiology, and molecular subtyping. Additionally, we elaborate on the latest research into mechanisms contributing to breast cancer progression, emerging treatment strategies, and long-term patient management. This review offers valuable insights into the latest advancements in Breast Cancer Research, thereby facilitating future progress in both basic research and clinical application.
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