Breast cancer is the most diagnosed cancer among women worldwide and represents a major global health burden due to its biological heterogeneity and variable clinical outcomes. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Molecularly heterogeneous and lacking targeted treatments, TNBC is associated with poor outcomes and high recurrence. This review evaluates the potential of CHEK1, TOP2A, and c-MET as biomarkers for companion diagnostics in TNBC. CHEK1 promotes DNA damage response and cell-cycle checkpoints, especially in p53-deficient tumours, and could serve as a predictive biomarker of sensitivity to CHEK1 inhibitors. TOP2A, which is involved in DNA replication and chromosomal segregation, is frequently overexpressed in highly proliferative TNBC and correlates with response to anthracycline-based chemotherapy. c-MET, a receptor tyrosine kinase, drives tumour progression, invasion, and therapeutic resistance; its overexpression is associated with poor clinical outcomes and has been linked to emerging targeted therapies. Collectively, CHEK1, TOP2A, and c-MET represent promising biomarkers for Companion diagnostic development in TNBC. However, further analytical validation, prospective clinical validation, and assay standardization efforts are needed prior to clinical use.
Retinoblastoma protein (pRb) is a critical tumor suppressor that regulates the cell cycle and maintains genetic stability. While mutations in the retinoblastoma 1(RB1) gene are well-documented in gastric adenocarcinoma (GAC) and hepatocellular carcinoma (HCC), the genomic landscape in Middle Eastern populations remains largely unknown. Thus, this study aimed to systematically characterize the entire spectrum of RB1 mutations in a large cohort of Iraqi patients with GAC and HCC. In a cohort of 885 patients (487 GAC and 398 HCC), genomic analysis was conducted. The study incorporated CRISPR-Cas9 knockout models, protein-protein interaction assays, pathway enrichment analysis, and machine learning for predictive modeling. Results showed higher rates of RB1 mutations in GAC (28.3%) and HCC (35.6%) compared to global averages (GAC: 12.1%; HCC: 8.7%) in the TCGA registry. Notably, GAC mutations predominantly affected the B-pocket domain (60.9%), while HCC mutations favored the A-pocket (62.7%). Dual RB1/p53 mutations were present in 71.2% of GAC and 38.9% of HCC patients. Functional studies revealed a significant activation of the DNA damage response in GAC (ATM/Chk2: 3.4-fold increase, p=1.2×10⁻⁸) and upregulation of the Wnt/β-catenin pathway in HCC (2.8-fold increase, p=3.7×10⁻⁶). Patient survival was notably lower in dual-mutant groups (GAC: HR = 2.67, 95% CI: 1.89–3.78; HCC: HR = 2.14, 95% CI: 1.52–3.01). The machine learning model accurately predicted therapeutic responses (89.3% accuracy), identifying heightened sensitivity to PARP inhibitors in RB1-mutant GAC (IC_50: 2.3 vs. 8.7 μM) and to CDK4/6 inhibitors in RB1-mutant HCC (IC_50: 3.1 vs. 12.4 μM). In conclusion, this study elucidates the RB1 mutational landscape in different cancers and highlights the therapeutic implications of these mutations in Iraqi patients, suggesting a synergistic role of RB1 and p53 mutations in gastric carcinoma, which indicates strategies for precision oncology tailored to Middle Eastern populations.
Enrofloxacin residues in poultry tissues may be exerting sub-inhibitory selective pressure on bacteria and contributing to antimicrobial resistance (AMR). The European Union has established Maximum Residue Limits (MRLs) for enrofloxacin in poultry of 100µg/kg in muscle, 200 µg/kg in liver, and 300 µg/kg in kidney (Commission Regulation (EC) No 508/1999). In this study, the residues of enrofloxacin in tissues of broilers after discriminate and indiscriminate use were measured for compliance with the EU MRLs as well as sub-inhibitory thresholds. Eighteen Cobb-500 broilers were distributed into three groups: Control (no antibiotic), Discriminate (10 mg/kg enrofloxacin for 7 days plus 7-day withdrawal) and Indiscriminate (continuous enrofloxacin until sacrifice). Residues of enrofloxacin in the liver, kidney, breast and thigh muscle were determined by a validated HPLC-UV method. Growth performance and blood parameters were assessed. The developed HPLC method showed good performance (r² > 0.999; recovery 86.7-91.2 %). The indiscriminate use resulted in violative residues above the EU MRLs in all tissues (liver: 1845 ± 212 µg/kg). Selective use resulted in no detectable residues in muscle but persistent residues in liver (45.2 ± 6.1 µg/kg) and kidney (18.5 ± 2.4 µg/kg), which were in compliance with EU MRLs but above the sub-inhibitory threshold of 10 µg/kg. No significant differences in growth and hematological parameters were found between groups. Following the recommended 7-day withdrawal time for poultry has removed any detectable residues from muscle, but sub-inhibitory concentrations of enrofloxacin will remain in the liver and kidney. Although all residues remaining after this period comply with EU MRLs, there may still be sufficient quantities of these residues present in liver and kidneys to create a selective pressure on bacteria. It is concluded that the results of this study could help formulate new guidelines about withdrawal times for critically important antimicrobials and develop guidelines for residue surveillance on the liver and kidney in broiler chickens. [ J Adv Biotechnol Exp Ther 2026; 9(3.000): 451-467]
Soybean oil (SO) is used worldwide, whereas mustard oil (MO) consumption is generally limited to South Asia. Nevertheless, the organ-damaging effects of these substances at multiple doses over time have not been well studied. This study evaluated the hematobiochemical and histopathological effects of SO and MO in a mouse model. A total of 84 male Swiss albino mice, aged 5 weeks, were divided into seven groups (n≤12 each): a control group (C) given pellets, and six treatment groups (S1-S3 and M1-M3) administered escalating doses of SO or MO at 15, 25, and 35 ml/kg for 60 days. Following euthanasia, blood samples were examined for hematological and biochemical parameters using standard assays. The hearts, livers, and kidneys were collected for measurement and then prepared for histopathology using H&E staining. The hematobiochemical parameters were significantly elevated in all treated groups when compared to the control group (P [ J Adv Biotechnol Exp Ther 2026; 9(3.000): 558-570]
Hyperlipidemia induces oxidative stress, leading to up-regulation of hepcidin, iron deposition, and impaired spermatogenesis. The current investigation examines the beneficial effects of Moringa oleifera leaf extract and atorvastatin on hyperlipidemia-induced physiological and histological changes in the testes of rats. Forty male rats were divided into eight groups, including: the control (G0), hyperlipidemia (G1), hyperlipidemia + moringa (G2), hyperlipidemia + atorvastatin (G3), hyperlipidemia + moringa with atorvastatin (G4), moringa (G5), atorvastatin (G6), moringa + atorvastatin (G7). For five weeks, rats were given either Moringa oleifera extract or atorvastatin. Serum hepcidin, catalase (CAT), glutathione peroxidase (GPx), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were assessed. Histological examination of iron deposition, sperm parameters, and DNA fragmentation index (DFI) were also evaluated. The outcomes demonstrated that the induction of hyperlipidemia resulted in a notable increase in 8-OHdG levels, hepcidin, iron deposition, and DFI, while there were significant decreased levels of CAT and GPx. There were also structural alterations in seminiferous tubules, significant reductions in Leydig, Sertoli, and germ cell populations, and impaired sperm. Interestingly, the combination therapy improved oxidative stress, iron homeostasis, histopathological features, and sperm quality. The combination of atorvastatin and Moringa oleifera exhibited synergistic effects in protecting against hyperlipidemia. Treating Moringa oleifera with atorvastatin is suggested to reduce hyperlipidemia-induced testicular damage. Studies should include larger sample sizes to assess the molecular mechanisms, particularly those that activate oxidative stress or affect iron metabolism. [ J Adv Biotechnol Exp Ther 2026; 9(3.000): 543-557]
