Lack of association between the eNOS rs1800779 (A/G) polymorphism and the myocardial infarction incidence among the Iraqi Kurdish population.

Objectives: The genetic polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are strongly associated with several cardiovascular diseases (CVDs) in various populations. The current study aimed to investigate the association of the eNOS rs1800779 (A/G) polymorphism with the progress of myocardial infarction (MI). Methods: Eighty-five healthy subjects and 80 patients with MI admitted to the Erbil Cardiac Centre in the Kurdistan Region of Iraq were enrolled in the study. All participants were Kurdish from the same ethnic group. The amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used to determine the rs1800779 (A/G) polymorphism of eNOS, and the nitric oxide (NO) serum level was detected by spectrophotometer. Results: The genotypic frequencies of the eNOS rs1800779 AA (wild type), AG, and GG were 58.75%, 33.75%, and 7.50%, respectively, in the MI patients, and 49.41%, 43.53%, and 7.06%, respectively, for the control group. The frequencies of the A and the G alleles were 75.6% and 24.4%, respectively, in the MI group, and 71.2% and 28.8%, respectively, in the control subjects. The results revealed a lack of association of the rs1800779 genotype distribution with the level of NO serum and increased risk of MI. Conclusion: The study concluded that there is a lack of association between the genotypes and alleles of the rs1800779 eNOS and susceptibility to MI in the studied population.

Association of Orai1 and Peizo1 genes expression with cellular proliferation, metastasis and angiogenesis biomarkers in colon tumor biopsies of CRC patients.

Colon cancer is a complex malignancy characterized by intricate molecular interactions that influence its progression. This study investigates the role of calcium channel gene expression (ORAI1 and Piezo1) and their interplay with angiogenesis-related genes (VEGFA, CCL3, and NF-KB1) in colon cancer tissue biopsies. Additionally, we explore the mutation profiles of pivotal oncogenes (KRAS, PI3KCA, and BRAF) and their potential correlations with calcium channel and angiogenesis-related gene expression. The results indicate significant upregulation of ORAI1 and Piezo1, suggesting their involvement in colon cancer pathogenesis. Correlations between ORAI1 and VEGFA/CCL3 highlight potential crosstalk between calcium signaling and angiogenesis. The mutation analysis identifies prevalent oncogenic mutations, while intriguing connections between gene expression and oncogenic mutations emerge. Notably, mutant KRAS exon 2 samples exhibit elevated CCL3 and VEGFA expression, suggesting a nuanced link between specific KRAS mutations and the tumor microenvironment. These findings illuminate the intricate molecular landscape of colon cancer and emphasize the potential roles of calcium channels, angiogenesis-related genes, and oncogenic mutations as prognostic markers and therapeutic targets.

Recent findings on the role of wild-type and mutant p53 in cancer development and therapy.

The p53 protein is a tumor suppressor encoded by the TP53 gene and consists of 393 amino acids with four main functional domains. This protein responds to various cellular stresses to regulate the expression of target genes, thereby causing DNA repair, cell cycle arrest, apoptosis, metabolic changes, and aging. Mutations in the TP53 gene and the functions of the wild-type p53 protein (wtp53) have been linked to various human cancers. Eight TP53 gene mutations are located in codons, constituting 28% of all p53 mutations. The p53 can be used as a biomarker for tumor progression and an excellent target for designing cancer treatment strategies. In wild-type p53-carrying cancers, abnormal signaling of the p53 pathway usually occurs due to other unusual settings, such as high MDM2 expression. These differences between cancer cell p53 and normal cells have made p53 one of the most important targets for cancer treatment. In this review, we have dealt with various issues, such as the relative contribution of wild-type p53 loss of function, including transactivation-dependent and transactivation-independent activities in oncogenic processes and their role in cancer development. We also discuss the role of p53 in the process of ferroptosis and its targeting in cancer treatment. Finally, we focus on p53-related drug delivery systems and investigate the challenges and solutions.

Nanoformulation of Polyphenol Curcumin Enhances Cisplatin-Induced Apoptosis in Drug-Resistant MDA-MB-231 Breast Cancer Cells.

Triple Negative Breast Cancer (TNBC) is the aggressive and lethal type of breast malignancy that develops resistance to current therapies. Combination therapy has proven to be an effective strategy on TNBC. We aimed to study whether the nano-formulation of polyphenolic curcumin (Gemini-Cur) would affect the cisplatin-induced toxicity in MDA-MB-231 breast cancer cells. MDA-MB-231 cells were treated with Gemini-Cur, cisplatin and combination of Gemini-Cur/Cisplatin in a time- and dose-dependent manner. Cell viability was studied by using MTT, fluorescence microscopy and cell cycle assays. The mode of death was also determined by Hoechst staining and annexin V-FITC. Real-time PCR and western blotting were employed to detect the expression of BAX and BCL-2 genes. Our data demonstrated that Gemini-Cur significantly sensitizes cancer cells to cisplatin (combination index ≤ 1) and decreases IC50 values in comparison with Gemini-cur or cisplatin. Further studies confirmed that Gemini-Cur/Cisplatin suppresses cancer cell growth through induction of apoptosis (p < 0.001). In conclusion, the data confirm the synergistic effect of polyphenolic curcumin on cisplatin toxicity and provide attractive strategy to attain its apoptotic effect on TNBC.

Vitamin K1 As A Potential Molecule For Reducing Single-Walled Carbon Nanotubes-Stimulated α-Synuclein Structural Changes And Cytotoxicity.

AIMS: Different kinds of vitamins can be used as promising candidates to mitigate the structural changes of proteins and associated cytotoxicity stimulated by NPs. Therefore, the structural changes of α-syn molecules and their associated cytotoxicity in the presence of SWCNTs either alone or co-incubated with vitamin K1 were studied by spectroscopic, bioinformatical, and cellular assays. METHODS: Intrinsic and ThT fluorescence, CD, and Congo red absorption spectroscopic approaches as well as TEM investigation, molecular docking, and molecular dynamics were used to explore the protective effect of vitamin K1 on the structural changes of α-syn induced by SWCNTs. The cytotoxicity of α-syn/SWCNTs co-incubated with vitamin K1 against SH-SY5Y cells was also carried out by MTT, LDH, and caspase-3 assays. RESULTS: Fluorescence spectroscopy showed that vitamin K1 has a significant effect in reducing SWCNT-induced fluorescence quenching and aggregation of α- syn. CD, Congo red adsorption, and TEM investigations determined that co-incubation of α- syn with vitamin K1 inhibited the propensity of α-syn into the structural changes and amorphous aggregation in the presence of SWCNT. Docking studies determined the occupation of preferred docked site of SWCNT by vitamin K1 on α- syn conformation. A molecular dynamics study also showed that vitamin K1 reduced the structural changes of α- syn induced by SWCNT. Cellular data exhibited that the cytotoxicity of α- syn co-incubated with vitamin K1 in the presence of SWCNTs is less than the outcomes obtained in the absence of the vitamin K1. CONCLUSION: It may be concluded that vitamin K1 decreases the propensity of α- syn aggregation in the presence of SWCNTs and induction of cytotoxicity.