Biomedicines

Background/Objectives: Ovarian cancer remains one of the most lethal gynecologic malignancies, primarily due to late diagnosis and the development of chemoresistance. Adriamycin (ADR) is effective but limited by systemic toxicity. Natural bioflavonoids such as hesperidin (Hes) may enhance chemotherapy efficacy through oxidative, apoptotic, and immune modulation. This study investigated the antiproliferative, pro-apoptotic, and immunomodulatory effects of Hes and ADR in human ovarian adenocarcinoma cells (SKOV3), focusing on Forkhead box P3 (FOXP3) and epidermal growth factor receptor (EGFR) signaling pathways. Methods: SKOV3 were treated with increasing concentrations of Hes (10–400 µM) and ADR (0.01–0.4 µM), either individually or in combination at their half-maximal inhibitory concentration (IC₅₀) ratios. Cell viability (MTT assay), gene expression (qRT-PCR), cytokine levels (ELISA), and total antioxidant capacity (TAC) were assessed to evaluate treatment responses. Results: Both agents reduced cell viability in a dose- and time-dependent manner, with the combination exhibiting synergistic cytotoxicity after 48 h. Co-treatment markedly upregulated Caspase-3 and Bax while downregulating FOXP3 and EGFR. Antioxidant capacity was significantly enhanced in the Hes-treated and combination groups (p < 0.001). Conclusions: Hes and ADR synergistically suppressed proliferation, induced apoptosis, and modulated cytokine balance by inhibiting FOXP3- and EGFR-mediated oncogenic signaling. This combination demonstrates strong potential as an adjuvant therapeutic strategy for ovarian cancer.

Long-COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are disabling diseases characterised by ongoing fatigue, post-exertional malaise, cognitive impairment, and autonomic dysfunction. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome typically follows viral infections, whereas Long-COVID exclusively follows SARS-CoV-2 infection, with overlapping but distinct features. This review uses comprehensive searches of online databases to compare their clinical presentations, pathophysiologies, and treatments. Both Long-COVID and ME/CFS appear to involve multifactorial mechanisms, including viral persistence, immune dysregulation, endothelial dysfunction, and autoimmunity, though their relative contributions remain uncertain. Symptom management strategies are consistent, however. Cognitive behaviour therapy has been successful, and there are minimal drug treatments. Graded exercise therapy occupies a contested place, recommending individualised pacing and multidisciplinary rehabilitation. Common and exclusive mechanisms must be identified to formulate valuable therapies. A more significant body of research focusing on immune dysfunction as a pathogenic mechanism for advancing the disease and enabling more effective therapies and diagnostics is needed.

Background: Cancer is a heterogeneous pathology, and among causative factors, gene expression can influence its development. Molecular approaches using extracellular vesicles (EVs) and non-coding RNAs (ncRNAs) offer great value in understanding tumor progression, early diagnosis, and potential therapies. Objectives: This systematic review was conducted in accordance with the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses guidelines. Its main objective was to evaluate the effects of cellular hypoxia in different types of cancer, exclusively using animal models and highlighting the regulatory role of microRNAs and circular RNAs in tumor development. Methods: A literature review was performed using the PubMed/Medline and Scopus databases without year limitations. The initial search yielded 171 articles. After applying the inclusion and exclusion criteria, 25 studies were included in this review. Data analysis showed that animal models provide detailed insights into different types of cancers under hypoxic conditions. Results: Our analysis identified that specific circRNAs, such as circPFKFB4 in breast cancer and circPDK1 in pancreatic cancer, are consistently associated with a worse prognosis and therapeutic resistance. Similarly, miRNAs such as miR-1287-5p (breast cancer) and miR-133a (colorectal cancer) have frequently been identified as tumor suppressors whose levels are altered by hypoxic conditions. Furthermore, the results suggested that in some cancers, the release of EVs may facilitate tumor progression and metastasis. However, manipulation of ncRNA expression causes significant changes in the tumor response, which suggests a therapeutic response. Conclusions: This study shows that the use of animal models is essential for exploring the molecular mechanisms of cancer and establishing new therapeutic approaches.