Molecular Design, Spectroscopic, DFT, Pharmacological, and Molecular Docking Studies of Novel Ruthenium(III)-Schiff Base Complex: An Inhibitor of Progression in HepG2 Cells.

A novel ruthenium(III)-pyrimidine Schiff base was synthesized and characterized using different analytical and spectroscopic techniques. Molecular geometries of the ligand and ruthenium complex were investigated using the DFT-B3LYP level of theory. The quantum global reactivity descriptors were also calculated. Various biological and molecular docking studies of the complex are reported to explore its potential application as a therapeutic drug. Cytotoxicity of the complex was screened against cancer colorectal (HCT116), breast (MCF-7 and T47D), and hepatocellular (HepG2) cell lines as well as a human normal cell line (HSF). The complex effectively inhibited the tested cancer cells with variable degree with higher activity towards HepG2 (IC50 values were 29 µM for HepG2, 38.5 µM for T47D, 39.7 µM for HCT, and 46.7 µM for MCF-7 cells). The complex induced apoptosis and cell cycle arrest in the S phase of HepG2 cells. The complex significantly induced the expression of H2AX and caspase 3 and caspase 7 gene and the protein level of caspase 3, as well as inhibited VEGF-A and mTOR/AKT, SND1, and NF-kB gene expression. The molecular docking studies supported the increased total apoptosis of treated HepG2 cells due to strong interaction of the complex with DNA. Additionally, the possible binding interaction of the complex with caspase 3 could be responsible for the elevated activity of caspase 3-treated cells. The score values for the two receptors were -3.25 and -3.91 kcal/mol.

Retraction: Predictors of Quality of Life Among People Living With Multimorbidity in Karachi, Pakistan: A Cross-Sectional Study.

[This retracts the article DOI: 10.7759/cureus.18803.].

Predictors of Quality of Life Among People Living With Multimorbidity in Karachi, Pakistan: A Cross-Sectional Study.

Introduction Multimorbidity is defined as the coexistence of more than one chronic condition in one individual. It is related to enhanced rates of disability and mortality, enhanced disease burden, decreased function levels, and it can affect the wellbeing and daily activities of people, including loss of autonomy and independence. The aim of the current study is to determine the predictors of quality of life among patients with multimorbidity in Karachi, Pakistan. Methodology It was a cross-sectional study conducted in 12 health care facilities of six districts in Karachi, Pakistan. Two health care facilities were selected from each district using a convenient sampling technique. The total sample size of this study was 690, equally distributed among 12 health care facilities. Results The majority of participants (33.47%) belonged to the age group of 40 to 49 years, while 29.85% of participants had an age between 30 to 39 years. More than half of the participants were females (50.87%). Overall, the multivariate analysis showed being male, married, younger, high educational status and employed were positively associated with quality of life. While having lower family income is negatively associated with quality of life. Conclusion The findings of this study had important implications for identifying distinct multimorbidity individuals who were at risk of a lower quality of life, and they emphasized the need for disease detection and treatment at an early stage. The study can also give important evidence for decision-makers when it comes to allocating health resources more efficiently, and health administrative departments can improve chronic disease management.

Purification and Characterization of Ornithine Decarboxylase from Aspergillus terreus; Kinetics of Inhibition by Various Inhibitors.

l-Ornithine decarboxylase (ODC) is the rate-limiting enzyme of de novo polyamine synthesis in humans and fungi. Elevated levels of polyamine by over-induction of ODC activity in response to tumor-promoting factors has been frequently reported. Since ODC from fungi and human have the same molecular properties and regulatory mechanisms, thus, fungal ODC has been used as model enzyme in the preliminary studies. Thus, the aim of this work was to purify ODC from fungi, and assess its kinetics of inhibition towards various compounds. Forty fungal isolates were screened for ODC production, twenty fungal isolates have the higher potency to grow on L-ornithine as sole nitrogen source. Aspergillus terreus was the most potent ODC producer (2.1 µmol/mg/min), followed by Penicillium crustosum and Fusarium fujikuori. These isolates were molecularly identified based on their ITS sequences, which have been deposited in the NCBI database under accession numbers MH156195, MH155304 and MH152411, respectively. ODC was purified and characterized from A. terreus using SDS-PAGE, showing a whole molecule mass of ~110 kDa and a 50 kDa subunit structure revealing its homodimeric identity. The enzyme had a maximum activity at 37 °C, pH 7.4-7.8 and thermal stability for 20 h at 37 °C, and 90 days storage stability at 4 °C. A. terreus ODC had a maximum affinity (Km) for l-ornithine, l-lysine and l-arginine (0.95, 1.34 and 1.4 mM) and catalytic efficiency (kcat/Km) (4.6, 2.83, 2.46 × 10-5 mM-1·s-1). The enzyme activity was strongly inhibited by DFMO (0.02 µg/mL), curcumin (IC50 0.04 µg/mL), propargylglycine (20.9 µg/mL) and hydroxylamine (32.9 µg/mL). These results emphasize the strong inhibitory effect of curcumin on ODC activity and subsequent polyamine synthesis. Further molecular dynamic studies to elucidate the mechanistics of ODC inhibition by curcumin are ongoing.