The novel anti-fibrillary effects of volatile compounds α-asarone and ß-caryophyllene on tau protein: Towards promising therapeutic agents for Alzheimer's disease.

The abnormal deposition of tau protein is one of the critical causes of tauopathies including Alzheimer's disease (AD). In recent years, there has been great interest in the use of essential oils and volatile compounds in aromatherapy for treating AD, since volatile compounds can directly reach the brain through intranasal administration. The volatile compounds α-asarone (ASA) and ß-caryophyllene (BCP) have revealed various important neuroprotective properties, useful in treating AD. In this study, the volatile compounds ASA and BCP were assessed for their effectiveness in preventing tau fibrillation, disassembly of pre-formed tau fibrils, and disaggregation of tau aggregates. SDS-PAGE and AFM analyses revealed that ASA and BCP inhibited tau fibrillation/aggregation and decreased the mean size of tau oligomers. Tau samples treated with ASA and BCP, showed a reduction in ThT and ANS fluorescence intensities, and a decrease in the ß-sheet content. Additionally, ASA and BCP disassembled the pre-formed tau fibrils to the granular and linear oligomeric intermediates. Treatment of neuroblastoma SH-SY5Y cells with tau samples treated with ASA and BCP, revealed protective effects as shown by reduced toxicity of the cells, due to the inhibition of tau fibrillation/aggregation. Overall, ASA and BCP appeared to be promising therapeutic candidates for AD.

Molecular interaction of fibrinogen with zeolite nanoparticles.

Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. Thus, we probed the molecular interactions between fibrinogen and zeolite nanoparticles using both experimental and simulation approaches. The results indicated that fibrinogen has a strong and thermodynamically favorable interaction with zeolite nanoparticles in a non-cooperative manner. Additionally, fibrinogen experienced a substantial conformational change in the presence of zeolite nanoparticles through a concentration-dependent manner. Simulation results showed that both E- and D-domain of fibrinogen are bound to the EMT zeolite NPs via strong electrostatic interactions, and undergo structural changes leading to exposing normally buried sequences. D-domain has more contribution in this interaction and the C-terminus of γ chain (γ377-394), located in D-domain, showed the highest level of exposure compared to other sequences/residues.

Colon Cancer and Specific Ways to Deliver Drugs to the Large Intestine.

BACKGROUND: It has been postulated that colon cancer is the third cause of cancer death worldwide. Recently, colon-targeted drug delivery systems have been developed for improving systemic drug delivery and treatment of local colon associated diseases. Using such drug delivery systems increases the drug's effectiveness and results in reduced systemic side effects. Drug delivery systems formulated for the colon requires that the triggering of drug release mechanism is designed based on the colon's physiological conditions. However, improving the site specificity and drug release kinetics of colon-targeted drug delivery systems is desired and is currently under active research. OBJECTIVE: This review discusses colon cancer along with various colon-targeted drug delivery systems such as pro-drug formation, pH-sensitive polymers, hydrogels, time-dependent release systems, bio-adhesive and nanoparticle systems. The aim is to understand the effect of using colon-targeted drug delivery systems on therapeutic effectiveness of the drug by improving its degradation and bioavailability. Colon targeting holds a great promise as a therapeutic approach but it still requires more innovation. CONCLUSION: The distribution of the drugs in the colon suffers from problems related to the pH, retention time, micro-flora, and degrading enzymes of gastrointestinal tract. Moreover, these drug delivery systems are capable of overcoming some of the limitations in common targeting approaches. A precise assessment of such systems needs the use of various assaying protocols in order to characterize their traits and clarify their design rationales.

Effect of two imidazolium derivatives of ionic liquids on the structure and activity of adenosine deaminase.

The effect of two ionic liquids, 1-allyl 3-methyl-imidazolium (IL1) and 1-octhyl 3-methyl-imidozolium chlorides (IL2), on the structure and activity of adenosine deaminase (ADA) were described by UV-vis and fluorescence spectrophotometry in phosphate buffer and results were compared with docking and molecular dynamics (MD) simulation studies. All results showed that inhibition of activity and reduction of enzyme tertiary structure are more for octhyl than allyl derivative due to the more hydrophobic property of it. Finally structure parameters obtained from MD simulation showed that ionic liquid reduces intermolecular hydrogen bond and unfold enzyme structure. Calculation results are in good agreement with spectrophotometric studies.