Genetic Polymorphisms of Xenobiotics-Metabolizing Enzymes Contributing to Leukemia

Polymorphisms in xenobiotic-metabolizing enzymes have been linked to an increased risk of developing leukemia (XMEs). XMEs are found in all higher organisms and are one of the first lines of defense against environmental chemicals. Toxins, including therapeutic agents, are completely metabolized and eliminated from the body by an enzyme system that is encoded by specific genes. The majority of these genes are polymorphic, and some of the polymorphic forms have altered enzyme activity. Phase I XMEs, such as cytochrome P450s (CYPs), and phase II biotransformation enzymes, such as glutathione S-transferases (GST), UDP-glucuronosyltransferases (UGT), and N-acetyltransferases (NAT), are the most important. The majority of genetic variation discovered during clinical testing is due to single-nucleotide polymorphisms (SNPs). The purpose of this chapter is to highlight information about of some genetic polymorphisms of XMEs, contributing to AML, ALL, CML, and ALL. Several keywords were used to search the databases PubMed, Google Scholar, and Web of Science. Currently, numerous manuscripts suggested that genetic polymorphisms of XMEs were associated with ALL, CLL AML, and CML susceptibility

Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

Chronic inflammation and reduced blood levels of omega-3 fatty acids (n − 3) are known characteristics of sickle cell disease (SCD).The anti-inflammatory properties of n − 3 fatty acids are well recognized. Omega-3 treated (n = 24), hydroxyurea (HU) treated (n = 18), and n − 3 untreated (n = 21) homozygous SCD patients (HbSS) and healthy (HbAA) controls (n = 25) matched for age (5–16 years), gender and socioeconomic status were studied. According to age (5–10) or (11–16) years, two or three capsules containing 277.8 mg docosahexaenoic (DHA) and 39.0 mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned to n − 3 treated and n − 3 untreated groups, respectively. Hydroxyurea treated group was on dosage more than 20 mg/kg/day. The effect of supplementation on systemic and blood cell markers of inflammation was investigated. The n − 3 treated group had higher levels of DHA and EPA (p < 0.001) and lower white blood cell count and monocyte integrin (p < 0.05) compared with the n − 3 untreated. No difference was detected between the two groups regarding C-reactive protein, granulocytes integrin and selectin, plasma tumour necrosis factor-α and interleukin-10. The n − 3 treated group had lowered nuclear factor-kappa B (NF-κB) gene expression compared to n − 3 untreated and HU treated groups (p < 0.05). This study provides evidence that supplementation with n − 3 fatty acids may ameliorate inflammation and blood cell adhesion in patients with SCD

Polyphenols and Their Nanoformulations: Protective Effects against Human Diseases

Polyphenols are the secondary metabolites synthesized by the plants as a part of defense machinery. Owing to their antioxidant, anti-inflammatory, anticancerous, antineoplastic, and immunomodulatory effects, natural polyphenols have been used for a long time to prevent and treat a variety of diseases. As a result, these phytochemicals may be able to act as therapeutic agents in treating cancer and cardiovascular and neurological disorders. The limited bioavailability of polyphenolic molecules is one issue with their utilization. For the purpose of increasing the bioavailability of these chemicals, many formulation forms have been developed, with nanonization standing out among them. The present review outlines the biological potential of nanoformulated plant polyphenolic compounds. It also summarizes the employability of various polyphenols as nanoformulations for cancer and neurological and cardiovascular disease treatment. Nanoencapsulated polyphenols, singular or in combinations, effective both in vitro and in vivo, need more investigation

The prevalence of haemoglobin variants in a Sudanese population : Haematological and molecular analysis

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Synthesis of zinc oxide (zno)-titanium dioxide (tio2)-chitosan-farnesol nanocomposites and assessment of their anticancer potential in human leukemic molt-4 cell line

Leukemia is the most prevalent cancer in children and one of the most common and deadly cancers that affect adults. Several metal oxide nanoparticles, biopolymers, and phytochemicals have been discovered to target cancer cells selectively while inflicting low to no damage to healthy cells. Among the existing nanoparticle synthesis methodologies, biologically synthesized nanoparticles using phytochemicals have emerged as a straightforward, economical, and environmentally sound strategy. The synergistic antitumor potential of ZnO-TiO2-chitosan-farnesol nanocomposites (NCs) against leukemia MOLT-4 cells was investigated in the current study. After synthesizing the NCs, characterization of the same was carried out using XRD, DLS, FESEM, TEM, PL, EDX, and FTIR spectroscopy. To analyze its anticancer activity, MOLT-4 cells were cultured and treated at diverse dosages of NCs. The cell viability upon treatment was examined by MTT assay. The morphological and nuclear modifications were observed by dual staining. ROS and MMP levels were observed by DCFH-DA staining and Rh-123 dye, respectively. Furthermore, the caspase 3, 8, and 9 levels were examined by performing ELISA. The XRD patterns exhibited a hexagonal structure of the NCs. In the DLS spectrum, the hydrodynamic diameter of the NCs was observed to be 126.2 nm. The electrostatic interface between the ZnO-TiO2-chitosan-farnesol NCs was confirmed by the FTIR spectra. A significant loss of cell viability in a dosage-dependent trend confirmed the cytotoxic effect of the NCs. An elevated ROS level and MMP depletion suggested apoptosis-associated cell death via the intrinsic pathway, which was confirmed by elevated expressions of caspase 3, 8, and 9 markers. Thus, the results showed that the synthesized NCs demonstrated a remarkable anticancer potential against leukemic cells and can be potentially valuable in cancer treatments. The findings from this study conclude that this is a new approach for modifying the physicochemical characteristics of ZnO-TiO2-chitosan-farnesol composites to increase their properties and synergistically exhibit anticancer properties in human leukemic cancer cells