Enhancing the Acyltransferase Activity of Candida antarctica Lipase A by Rational Design

A few lipases, such as Candida antarctica lipase A (CAL‐A), are known to possess acyltransferase activity. This enables the enzyme to synthesize fatty acid esters from natural oils and alcohols even in the presence of bulk water. Unfortunately, fatty acids are still formed in these reactions as undesired side‐products. To reduce the amount of fatty acids, several CAL‐A variants were rationally designed based on its crystal structure. These variants were expressed in Escherichia coli and Pichia pastoris, purified, and their acyltransferase/hydrolase activities were investigated by various biocatalytic approaches. Among the investigated variants, mutant Asp122Leu showed a significant decrease in the hydrolytic activity, thus reducing the side‐product yield during acylation. As desired, this variant retained wild‐type process‐relevant features like pH profile and thermostability.     

Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer

Cancer is a major cause of death, affecting human life in both developed and developing countries. Numerous antitumor agents exist but their toxicity and low efficacy limits their utility. Furthermore, the complex pathophysiological mechanisms of cancer, serious side effects and poor prognosis restrict the administration of available cancer therapies. Thus, developing novel therapeutic agents are required towards a simultaneous targeting of major dysregulated signaling mediators in cancer etiology, while possessing lower side effects. In this line, the plant kingdom is introduced as a rich source of active phytochemicals. The secondary metabolites produced by plants could potentially regulate several dysregulated pathways in cancer. Among the secondary metabolites, flavonoids are hopeful phytochemicals with established biological activities and minimal side effects. Flavonoids inhibit B-cell lymphoma 2 (Bcl-2) via the p53 signaling pathway, which is a significant apoptotic target in many cancer types, hence suppressing a major dysregulated pathway in cancer. To date, there have been no studies reported which extensively highlight the role of flavonoids and especially the different classes of flavonoids in the modulation of Bcl-2 in the P53 signaling pathway. Herein, we discuss the modulation of Bcl-2 in the p53 signaling pathway by different classes of flavonoids and highlight different mechanisms through which this modulation can occur. This study will provide a rationale for the use of flavonoids against different cancers paving a new mechanistic-based approach to cancer therapy.     

NS5ATP9 Contributes to Inhibition of Cell Proliferation by Hepatitis C Virus (HCV) Nonstructural Protein 5A (NS5A) via MEK/Extracellular Signal Regulated Kinase (ERK) Pathway

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a remarkable protein as it clearly plays multiple roles in mediating viral replication, host-cell interactions and viral pathogenesis. However, on the impact of cell growth, there have been different study results. NS5ATP9, also known as KIAA0101, p15PAF, L5, and OEACT-1, was first identified as a proliferating cell nuclear antigen-binding protein. Earlier studies have shown that NS5ATP9 might play an important role in HCV infection. The aim of this study is to investigate the function of NS5ATP9 on hepatocellular carcinoma (HCC) cell lines proliferation under HCV NS5A expression. The results showed that overexpression of NS5ATP9 inhibited the proliferation of Bel7402 cells, whereas knockdown of NS5ATP9 by interfering RNA promoted the growth of HepG2 cells. Under HCV NS5A expression, RNA interference (RNAi) targeting of NS5ATP9 could reverse the inhibition of HepG2 cell proliferation, suggesting that NS5ATP9 might be an anti-proliferation gene that plays an important role in the suppression of cell growth mediated by HCV NS5A via MEK/ERK signaling pathway. These findings might provide new insights into HCV NS5A and NS5ATP9.     

Synthesis of Nano‐γ‐Ferric Oxide by Thermolysis of the 2‐Mercapto‐5‐Methylpyridine‐N‐Oxide‐Iron(III) Complex via Factorial Design

2‐Mercapto‐5‐methylpyridine‐N‐oxide (MMPNO) and its sodium salt (NaMMPNO) were synthesized. The reaction of the latter with Fe³⁺ generates Fe(MMPNO)₃ chelate. The thermolysis of this chelate at 350 °C yielded highly pure reddish‐brown γ‐Fe₂O₃ nanocrystallites with an average particle size of 6.2 nm, a particle size range of 4.2 to 14.8 nm, and a specific surface area of 51.5 m²g^–1. The thermolysis process was optimized using the 2² fractional design. Quantitative tests and characterization of products were carried out by UV‐vis spectroscopy, XRD, LLS, SEM, TGA, BET, TEM, FT‐IR, elemental microanalysis, and classical analytical measurements.