Mashreq University

Thymidylate synthase (TS) is a folate-dependent enzyme essential for DNA synthesis and cell proliferation, making it one of the most enduring and clinically validated targets in anticancer chemotherapy. This review provides a comprehensive overview of TS structure, catalytic mechanism, and inhibition modes, emphasizing its central role in the action of classical antimetabolites such as fluoropyrimidines and antifolates. Despite decades of clinical success, drug resistance, toxicity, and limited tumor selectivity continue to challenge TS-targeted therapy. Recent advances in medicinal chemistry have introduced novel heterocyclic scaffolds, particularly oxadiazoles, pyrimidines, and their hybrid analogs, exhibiting improved TS inhibition, cytotoxic selectivity, and multitarget potential. Structure-activity relationship (SAR) analyses reveal key molecular features governing potency, including halogen substitution, π-π stacking interactions, and bioisosteric modifications. Moreover, innovative strategies such as noncatalytic enzyme destabilizers, hybrid multitarget inhibitors, and biomarker-guided prodrug systems are reshaping the future of TS-directed therapeutics. This review highlights the structural evolution of TS inhibitors from classical to next-generation agents, bridging mechanistic understanding with the design of safer and more effective anticancer drugs.

A novel panel of diselenide-linked imidazolone derivatives was synthesized and biologically profiled, revealing a promising new chemotype with broad-spectrum anticancer activity. Among the series, compounds 6b, 6d, and 6g demonstrated exceptional growth-inhibitory (GI) potency, achieving GI% values of 80.32%, 79.24%, and 86.40%, respectively—substantially outperforming doxorubicin (61.49%). Notably, 6g emerged as the lead candidate, exhibiting robust cytotoxicity across diverse cancer models with IC50 values of 6.49 µM (PC3), 6.58 µM (MCF7), 5.38 µM (A549), and 7.25 µM (HCT116). Mechanistic studies in A549 cells indicated that 6g simultaneously modulates multiple oncogenic pathways: it markedly downregulated CDK2, CDK4, and CDK6 (1.57–4.12 fold), while upregulating caspase-3, caspase-8, and caspase-9 (1.60–1.64 fold), collectively supporting its dual action on cell-cycle blockade and apoptotic activation. Furthermore, a 1.68-fold reduction in VEGFR-2 expression underscores its additional anti-angiogenic potential. Flow cytometry corroborated these findings, revealing a dramatic S-phase arrest, with the S-phase population rising from 4.61% to 42.09% upon treatment. Several other analogues, including 6d, 6e, 6i, and 6j, also displayed potent cytotoxicity (IC50 < 10 µM), highlighting the broader therapeutic relevance of this scaffold. Collectively, these data position 6g as a compelling multi-target anticancer lead that integrates apoptosis induction, cell-cycle regulation, and angiogenesis suppression—supporting its potential for development as a next-generation broad-spectrum anticancer agent.

The most frequent forms of α- and β-degenerate anaemias are characterized by disruption in the formation of globin protein, leading to defective hemoglobin synthesis known as thalassemia, a prevalent hereditary blood disorder. The present study aimed to diagnose hemoglobin A₂ (HbA₂) levels in patients with thalassemia in order to provide a reference for improving thalassemia control strategies. Data were collected from 155 thalassemia patients attending Baghdad Medical City between November 2024 and March 2025. Hematological parameters including red blood cell count (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hemoglobin A (HbA), hemoglobin A₂ (HbA₂), and fetal hemoglobin (HbF) were analyzed, and relationships among these parameters were evaluated. High-performance liquid chromatography (HPLC) results showed that thalassemia patients had significantly higher mean levels of HbA₂, HbA, and HbF (P ≤ 0.01) compared with the control group. Correlation analysis revealed no significant association between serum ferritin and RBC count in the HbA₂ patient group (P ≤ 0.01). The findings indicate that individuals with β-thalassemia trait typically exhibit normal serum ferritin levels, mildly elevated red blood cell counts, and increased HbA₂ levels.

Osteoid osteoma is the third most common benign bone tumor, composed of osteoid and woven bone that rarely exceeds 1.5 cm in dimension. The typical presentation is intense pain that mostly worsens at night and is relieved with non-steroidal anti-inflammatory drugs. X-ray is the initial imaging modality; however, CT scan is the modality of choice as it can identify almost all cases of osteoid osteoma. Our case demonstrates that the integration of O-arm navigation with arthroscopic visualization offers a novel and effective approach for managing subchondral osteoid osteomas. Although traditional surgical excision and CT-guided radiofrequency ablation have shown long-term high success rates, they are associated with more morbidity and cosmetically undesirable scarring. Our technique combines the benefits of both approaches while minimizing their respective limitations. This dual-modality approach proved particularly valuable in our young, active patient, where preservation of joint integrity and rapid return to function were paramount. The successful outcome suggests that this technique may represent a significant advancement in the surgical management of subchondral osteoid osteomas.

Objective: To determine the prevalence and types of oral mucosal lesions associated with fixed metal orthodontic appliances and assess their correlation with patient demographics and treatment duration. Materials and Methods: A cross-sectional study of 235 patients (aged 11-39 years) undergoing fixed orthodontic treatment was conducted in Baghdad, Iraq (September 2024-March 2025). Clinical examinations were performed by two specialists, and data were analyzed using SPSS version 22.0. Results: Among 235 participants (63.4% females, 80% aged &lt;25 years), gingivitis was most prevalent (61.3%), followed by ulcerative lesions (29.4%), white lesions (3.4%), fibroma (2.6%), infection (1.3%), and periodontitis (1.3%). Orthodontic treatment duration &gt;1 year was significantly associated with increased lesion prevalence (p=0.002). No significant gender-based differences were observed (p&gt;0.05). Conclusion: Fixed orthodontic appliances are associated with high prevalence of oral mucosal lesions, particularly gingivitis and ulcers. These findings emphasize the need for preventive strategies and comprehensive oral hygiene protocols in orthodontic care.

Background: Both hereditary and environmental factors play essential roles in the complex diseases collectively known as oral and maxillofacial diseases. The important role genetic factors play in susceptibility, development, and treatment outcome of all sorts of diseases has been highlighted. Advances in molecular biology over the last several years have made it clear. Materials and Methods: This study was conducted as a narrative literature review based on systematic searches across PubMed, Scopus, and Google Scholar databases. Relevant English-language articles published between 2015 and 2025 were selected using keywords such as genetic factors, oral and maxillofacial diseases, molecular mechanisms, oral cancer, and craniofacial anomalies. Results: The review revealed that several oral and maxillofacial disorders have strong genetic and molecular bases. Mutations in MSX1, IRF6, and TP63 were linked to cleft lip and palate, while AMELX, ENAM, and DSPP mutations contributed to hereditary enamel and dentin defects. In oral cancer, overexpression of oncogenes (EGFR, RAS) and inactivation of tumor suppressor genes (TP53, RB1) were frequently observed, alongside epigenetic alterations. Variants in inflammatory genes such as IL-1 and TNF-α were associated with increased susceptibility to periodontal diseases. Conclusions: It is crucial to understand the molecular and genetic causes of oral and maxillofacial diseases. Genetic testing is indispensable for personalized treatment, for assessing risks and for early detection of disease. Multi-omic research, gene therapy, and precision medicine advances all promise to transform the future patient care in oral and maxillofacial healthcare fields. No matter existing problems such as access, complexity or ethical, they have great prospects of accomplishment in time to save human costs.

A series of novel phthalimidoalkyl-arylidene thiazolidinedione hybrids (10a-e and 11a-e) were designed and synthesized by the combination of the bioactive phthalimide and thiazolidinedione pharmacophores and connected via an ethyl or propyl linker. Additionally, selenocyanates (12 and 13) were synthesized via nucleophilic substitution using KSeCN in DMF. The novel phthalimide benzylidene thiazolidinedione hybrids (10a-e and 11a-e) and phthalimide selenocyanates (12 and 13) were examined as apoptotic inducers against 15 cancer cell lines. Compound 10e showed the best mean growth inhibition percentage (GI%) of 64.60% compared with the FDA-approved doxorubicin (Dox). Moreover, the synthesized compounds showed higher therapeutic efficacy against the A549 and MDA-MB-468 cell lines compared with HeLa and FaDu cells. Analogs 10e, 11b, 11d, and 13 displayed the highest cytotoxic potential at the MDA-MB-468 cancer cells with IC50 values of 12.52, 13.16, 12.00, and 14.78 µM, respectively, in comparison to Dox (IC50 = 11.39 µM). Evaluation of the apoptotic and proinflammatory markers after treatment with analog 13 revealed upregulation of the proapoptotic Caspases 3, 8, and 9 and downregulation of the prosurvival proteins BCL-2, MMP2, and MMP9 by 1.27-, 6.71-, 2.00-, 2.26-, 2.31-, and 2.12-fold change, respectively. Furthermore, analog 13 showed the most significant downregulation of COX-2 and IL-1β protein expression, showing 2.08- and 2.34-fold changes, respectively. Finally, the molecular docking study against Caspase 6 demonstrated eligible binding affinities of the examined analogs. Overall, this study demonstrated that the synthesized compounds are promising apoptotic inducers and possess great potential as anticancer drugs.