Publications | Ahmed Massoud

Repurposing approved drugs as ferroptosis modulators: a critical review of clinical trials in cancer and neurodegeneration

Fri, 19 Jun 2026 00:00:00 +0000

Abstract

Ferroptosis is a regulated form of cell death that depends on iron and is marked by lipid peroxidation and the inactivation of glutathione peroxidase 4. It has emerged as a pathway of broad relevance to cancer and neurodegenerative disease. Preclinical studies have identified potent ferroptosis inducers (System Xc⁻ and GPX4 inhibitors) and inhibitors (liproxstatin/ferrostatin derivatives, FSP1–CoQ10 activators) with promising therapeutic potential. However, clinical translation remains limited. Since dedicated therapeutics targeting ferroptosis are still in early development, current clinical evidence mainly comes from drug repurposing, approved drugs whose ferroptosis-modulating properties were discovered retrospectively after their initial approval. None of these completed trials used ferroptosis-specific pharmacodynamic data or prospectively tested ferroptosis as the primary therapeutic mechanism. Instead of just reclassifying these trials, this review introduces a four-category failure-mode framework, mechanism mismatch, biomarker absence, model-to-trial prediction, and target non-selective compound, to explain why preclinical signals of ferroptosis have yet to translate successfully. We conclude that progress depends on three developments: targeted modulators (purpose-developed or repurposed with confirmed engagement), proof-of-mechanism trials using ferroptosis-related endpoints, and patient selection aligned with precision medicine.

Cite this article: Zayed, M., Massoud, A., Elwakeel, E. et al. Repurposing approved drugs as ferroptosis modulators: a critical review of clinical trials in cancer and neurodegeneration. Naunyn-Schmiedeberg’s Arch Pharmacol (2026).

Betanin from 𝘉𝘦𝘵𝘢 𝘷𝘶𝘭𝘨𝘢𝘳𝘪𝘴 Attenuates Complete Freund’s Adjuvant-Induced Inflammatory Pain: Integrated Preclinical and In Silico Insights

Wed, 27 May 2026 00:00:00 +0000

Abstract

Background/Objectives: Betanin (BET), a prominent phytochemical mainly derived from Beta vulgaris, exhibits strong anti-inflammatory and antioxidant activities owing to its distinctive chemical structure. Nevertheless, its potential analgesic effect in the context of inflammatory pain remains insufficiently explored. Accordingly, this study investigated the analgesic effects of BET in a complete Freund’s adjuvant (CFA)-induced rat model of inflammatory pain. Methods: Rats received a single subcutaneous injection of 100 µL CFA to induce inflammatory pain, followed by oral administration of BET at doses of 40 or 80 mg/kg/day for 14 days. Results: BET treatment significantly reduced paw edema and improved HPL (hot plate latency) in CFA-injected rats. Biochemically, in the ipsilateral spinal cord of rats, BET at both 40 and 80 mg/kg significantly increased IL-4, and only the 80 mg/kg dose significantly reduced oxidative stress (MDA) and IL-1β. TNF-α levels were slightly reduced at both doses and did not reach statistical significance versus CFA. At the molecular level, miR-107 was significantly downregulated by BET at 80 mg/kg (but not 40 mg/kg), while miR-145 was significantly upregulated by both 40 mg/kg and 80 mg/kg compared to CFA. Pearson’s correlation indicated that miR-107 was positively correlated with MDA, IL-1β and TNF-α but negatively with IL-4, whereas miR-145 was positively correlated with IL-4 but negatively with IL-1β. PCA biplot analysis corroborated these findings, showing simultaneous presence of MDA, IL-1β, TNF-α, and miR-107 with CFA, and IL-4 and miR-145 were only related to control and CFA+BET80 groups. In addition, using transmission electron microscopy imaging, we found that BET alleviated neuronal damage in CFA-treated rats. Furthermore, molecular docking analysis predicted that BET may exhibit stable binding interactions with several inflammation- and apoptosis-related targets, including AKT1, mTOR, IKKβ, TNF-α, IL-1β, COX-2, caspase-3, caspase-7, and caspase-8, supporting its multi-target anti-inflammatory and antiapoptotic effects. Conclusions: Overall, our data suggest that BET can possibly exert analgesic effects in CFA-induced inflammatory pain by modulating oxidative stress and favoring a shift toward an anti-inflammatory status. These effects coincided with downregulation of miR-107, overexpression of miR-145, and improvements in inflammatory pain behaviors. Further investigations are required to validate the involvement of specific miRNA- and pathway-mediated effects. Nevertheless, our findings highlight BET as a promising natural candidate for future development of anti-inflammatory and analgesic strategies.

Cite this article: Massoud, A., Essawy, A. E., Alfredan, M. A., Abdel-Moneim, A. M., Gomaa, R. A., & Abdel Salam, S. (2026). Betanin from Beta vulgaris Attenuates Complete Freund’s Adjuvant-Induced Inflammatory Pain: Integrated Preclinical and In Silico Insights. Biomedicines, 14(6), 1202.

Integrating Single-Cell Sequencing and Proteomics to Unravel Stem Cell Heterogeneity: Implications for Precision Regenerative Medicine

Thu, 09 Apr 2026 00:00:00 +0000

Abstract

Stem cell populations are inherently diverse, consisting of distinct subtypes with unique molecular signatures, self-renewal capacities, and differentiation potentials. This natural variability complicates their clinical use, leading to unpredictable treatment outcomes and safety concerns in regenerative medicine. Traditional bulk analysis methods obscure this vital cellular diversity by providing average data. Therefore, studying stem cell heterogeneity at the single-cell level is crucial for developing reliable and precise therapeutic strategies. This review examines how integrating single-cell sequencing with proteomics technologies enhances the current understanding of stem cell biology. We discuss how single-cell RNA sequencing reveals transcriptomic diversity, identifies rare subpopulations, and traces lineage pathways. Additionally, we highlight emerging single-cell proteomic techniques, such as mass cytometry and high-sensitivity mass spectrometry, which directly analyze functional protein expression and signaling networks that ultimately define cellular phenotypes. Combining these methods provides a comprehensive view of stem cell states, offering insights into the molecular mechanisms that influence fate decisions and responses to external signals. Ultimately, these advances enable precision regenerative medicine by improving cell characterization and developing tailored differentiation strategies for safe and effective clinical applications.

Cite this article: Zayed, M., Massoud, A., Al-Haddad, R. et al. Integrating Single-Cell Sequencing and Proteomics to Unravel Stem Cell Heterogeneity: Implications for Precision Regenerative Medicine. Stem Cell Rev and Rep (2026).

Harnessing Adipose Ferroptosis: A Promising Novel Pathway for Obesity Treatment

Sat, 25 Oct 2025 00:00:00 +0000

Abstract

This review summarizes the potential of targeting ferroptosis-iron-dependent lipid peroxidation-as a novel strategy for treating obesity and its metabolic complications through mechanisms different from traditional interventions. Recent preclinical studies show that selectively inducing ferroptosis in lipid-rich adipocytes and obese mice can effectively decrease fat mass and enhance metabolic health. These ferroptosis-based methods target the fundamental cellular processes of adipocyte dysfunction, affecting lipid metabolism and reducing oxidative stress. The strategy appears promising in addressing major metabolic issues such as insulin resistance and hepatic steatosis. In addition, the ability to customize ferroptosis inducers based on individual metabolic profiles offers a pathway to highly personalized obesity treatments. Ferroptosis agonists offer a revolutionary therapeutic approach for obesity treatment by directly reducing fat mass and targeting key metabolic issues. However, applying these findings in clinical settings requires careful evaluation of the long-term safety and effects of pharmacological ferroptosis induction. This review highlights important gaps in current knowledge and suggests future research directions crucial for developing these innovative therapies.

Cite this article: Zayed, M., Massoud, A., Hassan, F. et al. Harnessing Adipose Ferroptosis: A Promising Novel Pathway for Obesity Treatment. Curr Obes Rep 14, 74 (2025).