BACKGROUND:Metastasis drives mortality in breast invasive carcinoma. We sought miRNA biomarkers that (i) discriminate metastatic potential, (ii) stratify prognosis, and (iii) translate into a clinically useful PFI predictor. METHODS:We analyzed 858 TCGA-BRCA primary tumors (20 M1, 838 M0). After filtering low-expression miRNAs, DESeq2 identified 10 miRNAs downregulated in M1. Class imbalance was addressed with ADASYN; Random Forest and XGBoost feature importance over 50 iterations converged on four candidates (hsa-miR-150, -5694, -6510, -7156). Ten ML models (single learners and ensembles) were trained with nested tuning and evaluated on balanced test sets and the original cohort. Prognostic value was tested by Kaplan-Meier and Cox regression across OS, DSS, DFI, and PFI. Endpoint-specific Cox β-coefficients yielded miRNA risk scores; a PFI nomogram combined the PFI score with N and M stage. We profiled miR-150, its isoforms (3p/5p), and the three additional candidates in cell lines (MCF-7, MDA-MB-231) and in a 4T1 murine model with histologic confirmation of lung metastasis. Circulating/metastasis-related biomarkers (LDH/PDH ratio, VEGF, Angiopoietin-2, MMP-2) were assayed in serum. RESULTS:Ensembles showed near-perfect discrimination on balanced data and strong transfer to the original cohort (test AUCs: Bagging ≥0.979, Random Forest 0.981; original-cohort XGBoost 0.973 ± 0.008). High expression of miR-150 and miR-6510 associated with longer OS and DSS; for PFI, miR-150, miR-6510, and miR-5694 were favorable. The three-miRNA PFI score independently predicted progression (multivariable HR = 1.85; 95 % CI: 1.14-3.01) and, integrated with N and M stage, improved 3- and 5-year PFI discrimination (AUC 0.68 and 0.70) with robust calibration. Experimentally, miR-150 (3p/5p) declined in metastatic tissues and blood, while metastatic mice showed elevated LDH/PDH, VEGF, Ang-2, and MMP-2, supporting a mechanistic axis linking miRNA suppression, metabolic rewiring, angiogenesis, and matrix remodeling. CONCLUSIONS:An integrative pipeline identifies a four-miRNA signature associated with lung metastasis and delivers a translational PFI nomogram. Concordant experimental data and serum biomarkers reinforce biological plausibility and clinical potential, including liquid-biopsy applications.

Garlic (Allium sativum) contains bioactive components with antioxidants and anti-inflammatory constituents with potential anticancer activity. We aimed to compare a petroleum-ether garlic extract (PEGE) versus an ethanolic garlic extract (EGE) in a DMBA-induced murine hepatic carcinogenesis model. Fresh garlic was extracted with petroleum ether or ethanol and chemically characterized by GC–MS. PEGE was enriched in long-chain fatty acids/derivatives, while EGE contained both lipids and more polar constituents. Male Swiss albino mice received DMBA and were assigned to concurrent (DMBA + extract) or post-DMBA (DMBA → extract) regimens; extract-only and vehicle groups served as toxicity controls. Biochemical parameters (ALT, AST, AFP), oxidative stress markers (MDA, GSH), inflammatory signaling (NF-κB by ELISA), apoptosis (caspase-3 gene expression by qPCR), proliferation (PCNA by flow cytometry), and histopathological changes (H E staining) were evaluated. Extract-only showed no significant differences compared to control groups, indicating no overt toxicity. DMBA administration resulted in significant hepatic injury, evidenced by elevated liver enzymes and AFP, increased lipid peroxidation and NF-κB levels, depleted GSH, enhanced cellular proliferation, and severe histopathological alterations. Across endpoints, the post-DMBA PEGE regimen produced the largest overall normalization, followed by EGE. Post-treatment outperforming concurrent dosing for both extracts. Histology aligned the biochemical trends, showing reduced necrosis, inflammation, vascular congestion, and dysplastic changes in treated groups. Both garlic extracts showed hepatoprotective effects in this preclinical model; they were well tolerated and mitigated DMBA-induced injury, with PEGE given after DMBA yielding the strongest biochemical, molecular, and histopathological improvements. Chemical differences between the lipid-rich PEGE and the more polar EGE likely contribute to their differential efficacy and merit further standardization and mechanistic study.

Bladder cancer (BC) is one of the most frequent malignancies of the urinary tract. This study aimed to investigate the association between angiotensin-converting enzyme (ACE) I/D polymorphism (rs1799752) and bladder cancer risk in Egyptian patients. Bladder cancer cases (n = 140) were diagnosed based on cystoscopy and confirmed by histopathological examination of biopsies. Fifty sex- and age-matched healthy individuals served as controls. Peripheral blood was used to extract the genomic DNA, and the ACE I/D (rs1799752) polymorphism was genotyped using polymerase chain reaction (PCR). Genotype frequencies were comparable between groups (II:12

Pre-eclampsia constitutes a pregnancy disease characterized by hypertension and proteinuria, as well as dysregulation of the coagulation cascade and hypo fibrinolysis that affects many systems. The purpose of this study is to examine the connection between (-657 4G/5G PAI-1) and the danger of preeclampsia in Egyptian females. A case-control study included 140 Egyptian pregnant women with PE along with 100 normotensive women. The study includes extracting genomic DNA from blood, detecting SNP with ARMS-PCR, and assessing metabolic parameters with serum samples. The study discovered significant variations in PAI-1 5G/4G polymorphism between sufferers and the control group in general (P < 0.001), dominant (P = 0.004), and recessive models (P = 0.009). Pre-eclamptic women had lower SOD activity and GSH levels but higher MDA and GPx activities than the normotensive pregnant group. This study indicated that the − 657 4G/5G PAI-I mutation is substantially linked to the development of PE in Egyptian women.

Cancer kills 10 million people worldwide. In traditional medicine, antioxidant and anticancer plants are used for many ailments. Examining the effectiveness of olive leaf extract and ginger extract in eradicating mice. The main objective of this study was to establish an Ehrlich ascites carcinoma (EAC) tumor model. Eighty mice were separated into eight groups (n = 10) normal control, and (EAC control, standard, OLET, OLAQ, GE, OLAQ+GE, and OLET+GE) that are given 150 mg/kg of the extracts daily for 14 days after tumor induction. The mice were sacrificed, and serum and tissues were collected. All groups were tested for biochemical parameters, cell cycle progression, P53 gene expression, and interleukin-10 levels. Oral olive leaf extract (OLE) and ginger extract (GE) significantly reduced IL-10 levels. The treated groups had increased p53 gene expression and apoptosis. Compared to EAC mice, olive leaf and ginger extracts show in vivo anticancer efficacy and normalize biochemical marker levels. The GC/MS results for the chemical extracts of aqueous and ethanolic olive and ethanolic ginger plants confirmed and endorsed the results of the biological effect assay, with olive leaves and ginger having a greater phenolic content suppressing EAC growth more effectively.

Background and Aims Thyroid cancer, a prevalent endocrine malignancy, often presents as thyroid nodules, whose benign or malignant nature is challenging to determine. This study aims to identify circulating miRNA panels that may distinguish between benign nodules, papillary thyroid cancer, and normal thyroid conditions, building on extensive research into miRNAs as potential thyroid cancer biomarkers. Materials and Methods As a cross-sectional case-control study the study revealed the quantification of the 17-miRNA panel was evaluated using qRT-PCR method on 60 blood samples, comprising 25 patients diagnosed with PTC, 24 patients with benign lesions, and 11 healthy controls. Results We found that seven miRNAs, including miR144-3p and miR190a-5p, exhibited statistically significant variations in their expression levels, and miR144-3p exhibited the most superior diagnostic capability in distinguishing between malignant and healthy groups, as well as between benign and healthy groups. The concurrent utilization of miR144-3p, miR148a-3p, and miR190a-5p resulted in an enhancement of sensitivity from 76% to 88%. Conclusion Our study suggests that miR144-3p and miR190a-5p exhibit potential as biomarkers for distinguishing between benign and malignant thyroid nodules and healthy individuals, and further investigation is necessary to evaluate their clinical significance.

Abstract Introduction: Pre-eclampsia (P-EC) is a multisystem disorder of pregnancy, characterized by new-onset hypertension and proteinuria. Deregulation of the coagulation cascade and hypofibrinolysis appears to play a role in the development of P-EC. Methods: About 140 Egyptian pregnant women with a diagnosis of P-EC (patients' group) and 100 normotensive pregnant women not complicated by P-EC (a healthy control group) were collected. The genomic DNA was extracted from peripheral blood. Single-nucleotide polymorphisms were genotyped using ARMS-PCR. The serum was used for biochemical parameters measurement. Results: There is a strong significant (P < 0.0001) difference between PAI-1 5G/4G polymorphism among the patients and the control groups in the codominant model, high significant (P = 0.004) in the dominant model, high significant (P = 0.009) in the recessive model. Additionally, superoxide dismutase activity and reduced glutathione levels were decreased in pre-eclamptic women when compared to normotensive ones. On the other hand, malondialdehyde and glutathione peroxidase levels were increased in the pre-eclamptic group when compared with normalized pregnant ones. Conclusion: Our results showed that the mutated PAI-15G/4G polymorphisms may be associated with the development of P-EC in Egyptian women.

The liver is a unique organ in the human body. Many vital functions are attributed to it. Hepatitis C is one of the most diseases which intimidate liver integrity. ITPA is a human Inosine Triphosphate Pyrophosphatase (ITPase), which cleaves inosine triphosphate (ITP) and xanthine triphosphate (XTP) as well as their deoxyribose forms into monophosphates. Tumor necrosis factor receptor superfamily member 10A, is a cell surface receptor that bind to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and mediate the extrinsic pathway of apoptosis. We aimed to clarify the association between the single nucleotide polymorphism of ITPA and TNFSF10A with the outcome of HCV infection. A total of 264 subjects were recruited and classified into three main groups categorized as (I) spontaneous viral clearance (SVC) (N=55), (II)chronic HCV patients (CHCV) (N=106), and (III) control negative (N=103) where they were genotyped for SNP ITPA and TNFSF10A using allelic discrimination real-time PCR. The carriage of the C allele of ITPA rs7270101 was significantly higher in HCV group compared to that of SVC (odds ratio [OR] 1.6176) and to that of controls (1.8447) (both P < 0.01) and carriage of C allele of TNFRSF10A (rs20575) was significantly higher in HCV group compared to that of SVC (odds ratio [OR] 2.1691 and to that of controls (2.1953). Persistence of HCV infection is associated with C alleles of ITPA (rs7270101) and TNFRSF10A (rs20575) in Egyptian populations.

Hepatocellular carcinoma (HCC) is a lethal disease, and in HCC advanced stages, there is limited therapeutic efficacy. HCC results in a complication of fibrosis or cirrhosis. In this study, the protective effect of curcumin and selenium versus hepatocellular carcinoma caused by CCl4 in experimental animals was investigated. In all, 70 mice were divided into seven groups to study the effect of curcumin and selenium on CCl4-induced hepatocellular carcinoma. After treatment time, different animal groups were sacrificed, serum and liver samples were collected and processed for assay of biochemical and molecular parameters. Our results showed that CCl4 administration induced various alterations such as significant elevation in the serum levels of ALT, AST, and hepatic contents of malondialdehyde (MDA), and depletion in the levels of antioxidant parameters. CCl4 induced apoptosis in the hepatic cells indicated by an increased level of p53, CD4, CD8, Bax, and Annexin V/PI in addition to significant decrease in the level of Bcl-2. Administration of curcumin and selenium restored this abnormal variation in these biochemical parameters to normal values. Our study addressed that curcumin or selenium may be helpful in the protection against liver damage induced by CCl4. The hepatoprotective impact of curcumin or selenium might be mediated primarily by its potent antioxidant activity. Practical applications Hepatocellular carcinoma (HCC) ranked third common cause of death, primary liver cancer. Exposure to CCl4 was found to induce significant hepatotoxicity, characterized by fibrosis, bile duct proliferation, cirrhosis, and reduced hepatic function The work was prepared to investigate the protecting capacity of curcumin, selenium alone, and in combination against HCC induced by CCl4 in the experimental animal model. This study proved the protective effect of curcumin and selenium, alone and in combination with each other, where curcumin showed multiple pharmacological activities, including anti-inflammation and antioxidant, and have an essential role in inhibiting the progression of HCC.

IntroductionMethomyl (MET) is a monomethyl carbamate insecticide that is widely used around the world. MET is highly toxic to humans via oral exposure and mainly affects the liver tissue. It actually induces toxicity through overproduction of Reactive Oxygen Species (ROS) leading to oxidative stress with subsequent destruction of lipids, proteins, and nucleic acids.Materials and MethodsVarious plant extracts have been primarily screened for their antioxidant activities by measuring the free radical scavenging ability. Later, the plant extract with the highest antioxidant efficacy has been further formulated into a nanosuspension and the antioxidative effect has also been investigated against MET. Additionally, liver, kidney, and heart function biomarkers, liver tissue oxidative stress parameters, and total antioxidant capacity were assessed. Moreover, RT-PCR was applied to measure the Nrf2 expression.ResultsThe antioxidant screening data showed that balanites extract (BLT, Balanites aegyptiaca) had the most potent antioxidant activity. Besides, BLT showed dose-dependent improvement in liver, heart, and kidney functions in experimental mice treated with MET. The antioxidant biomarkers in liver tissue and total antioxidant capacity were elevated as compared to the MET-treated group. Furthermore, BLT significantly ameliorated MET-induced toxicity via the induction of Nrf2 and MET hepatic clearance. This study suggests the potential use of BLT extract as a natural antioxidant for the safe management of MET-induced hepatotoxicity and oxidative stress.ConclusionsBased on the presented data in this study, it can be concluded that BLT or BLT-NS can be used as a safe drug for methomyl toxicity.

ABSTRACT Endometrial hyperplasia (EH) is found to be a common diagnosis in women presenting with abnormal uterine bleeding, in advanced stages leading to cancer. To test the association of endometrial hyperplasia with the lymphotoxin-α (LT-α) C804A polymorphism, a case–control study was performed in Egyptian subjects. The cases comprised 100 endometrial hyperplasia patients, and the controls were 120 females served as control. Results showed that C allele versus A allele was compared in Simple Endometrial hyperplasia (SEH) cases compared to controls, there was no significant difference. In pre-menopausal cases, using the CC genotype as the reference genotype, the CA genotype was associated with a significantly elevated OR of 3.36 (95% CI =1.3–8.2, P = 0.007) in SEH cases compared to control. In addition, dominant genotypes (AA plus CA) were significantly increased in SEH cases compared to controls (OR =0.36, 95% CI =0.15–0.84, P =0.01). In conclusion, the common Lymphotoxin- α C804A polymorphism gene is associated with an increased risk of simple endometrial hyperplasia.

Background: Adiponectin gene polymorphisms have recently been reported to be associated with obesity. In Egypt, obesity has expanded especially with the changing nourishment propensities and the inexorably inactive ways of life, with almost 70 percent of the Egyptian populations being obese. Aim: To assess the relationship of the adiponectin gene (ADIPOQ) polymorphism in patients with Obesity in Egyptians. Subjects and methods: This study included 100 patients with obesity and 97 random controls. Results: Adiponectin rs1501299 polymorphism showed significant difference cases with different obesity grades where the T/T genotype was relatively higher in higher classes of obesity (Class II and III; (66.7% and 55.6% respectively, p = 000), which determines the susceptibility to obesity. Conclusion: Adiponectin rs1501299 polymorphism might be a candidate gene, which determines the susceptibility to obesity. Larger studies are necessary to confirm these findings in various populations.

In this study, a natural polymer, chitosan (CS) has been converted through modified procedures to produce a water-soluble nontoxic form that has been evaluated as a novel potential antitumor drug. CS was carboxymethylated and then further modified in mild aqueous medium via graft copolymerization using a new simple and reproducible method. The synthesized new derivative of carboxymethylated CS (DCMC) was fully characterized by numerous techniques including Fourier transform infrared spectroscopy (FT-IR), elemental analyzer (EA), scanning electron microscopy (SEM), two-dimensional wide-angle X-ray scattering (2D-WAXS), and differential scanning calorimetry (DSC). The anticancer activity of the DCMC was investigated using mice bearing Ehrlich ascites tumor cells (EAC) at different doses dissolved in isotonic saline. It has been found that treatment with DCMC significantly inhibited tumor growth in a dose-dependent manner. To better understand the molecular mechanism explaining the DCMC effect on cancer cells, we tested the response of EAC cells in vivo to DCMC using flow cytometry cell cycle analysis. The cell cycle analysis revealed a G(2)/M phase accumulation as well as a significant increase in sub-G 1 phase cells after treatment with DCMC. This indicates an induction of apoptosis in EAC cells associated with a highly significant decrease in tumor volume. In general, our results indicated that the DCMC is a regulator of tumor cell growth and differentiation not only by causing G(2)/M cell cycle arrest but also inducing their apoptotic death. Moreover, the estimated hematological profile such as hemoglobin, RBCs, as well as WBCs counts revealed normal levels in mice treated with DCMC, indicating the possibility of using the DCMC in cancer chemotherapy without causing anemia like other drugs. Biochemical assays also revealed that treatment with DCMC has led to an augmentation of the antioxidant defense system without affecting lipid peroxidation in EAC-bearing mice.

We have synthesized a novel 5-aminolevulinic acid (ALA) ester derivative from reacting ALA with β-citronellol and tested its potential for treatment of tumors by photodynamic therapy (PDT) in comparison to the widely used agents, ALA and Me-ALA (the methyl ester of ALA). The β-citronellol-ALA ester derivative was far superior to ALA in causing complete destruction of solid skin tumors after PDT treatment. Ex vivo PDT treatment of Ehrlich as cites carcinoma (EAC) cells indicated that the novel ester was effective in causing cell death and inhibition of cell growth, while flow cytometry studies revealed G0/G1 cell cycle arrest during the PDT-mediated response. Inoculation of healthy animals with EAC cell preparations extracted from tumor-bearing animals treated with various agents and then subjected to PDT treatment ex vivo revealed that the novel ester derivative was a significantly better agent than either ALA or Me-ALA at preventing or inhibiting growth of tumors in the inoculated animals. The findings suggest that the novel β-citronellol-ALA ester derivative offers a promising therapy for the treatment of apoptosis-reluctant tumors such as malignant tumors and may be superior to ALA or Me-ALA in PDT applications. Key words: Cancer, PDT, ALA, β-citronellol-ALA ester derivative, flow cytometry, tumor apoptosis, ALA-PDT.