Inhibitory effects of thymol and carvacrol on heme degradation and oxidative products due to tartrazine: In silico and in vitro studies.

The pathology of many diseases arises from oxidative stress and cell destruction. Antioxidant application is one of the most important ways for oxidative stress prevention in the cells and its consequent effects. The present study investigated the natural antioxidants inhibitory effects of thymol and carvacrol on human hemoglobin treated with tartrazine. Purified hemoglobin from human blood samples was treated with tartrazine alone or in combination with mentioned natural antioxidants (thymol and carvacrol). Treated samples were picked up at regular time intervals and changes were followed by UV-visible and fluorescence spectroscopic assays, and circular dichroism spectroscopy (CD). The result of fluorescence spectroscopy revealed that thymol and carvacrol prevented the production of heme-degradation products and advanced glycation end products (AGEs) caused by hemoglobin oxidation with tartrazine. The results of UV-visible and fluorescence spectroscopy revealed the positive effect of these antioxidants on preserving Hb folding, heme, and especially the porphyrin ring surrounding the microenvironment. The results of the circular dichroism (CD) assay showed the protection of alpha helix structure in hemoglobin treated with thymol and carvacrol compared to the control sample. The mentioned antioxidants caused hemoglobin resistance against tartrazine's destructive effect by preventing both heme degradation and glycemic toxins formation and thus reducing the rate of oxidative processes. This matter can be important for various pharmaceutical, health, and cosmetic industries.

Cell-Penetrating Peptides: As a Promising Theranostics Strategy to Circumvent the Blood-Brain Barrier for CNS Diseases.

The passage of therapeutic molecules across the Blood-Brain Barrier (BBB) is a profound challenge for the management of the Central Nervous System (CNS)-related diseases. The ineffectual nature of traditional treatments for CNS disorders led to the abundant endeavor of researchers for the design the effective approaches in order to bypass BBB during recent decades. Cell-Penetrating Peptides (CPPs) were found to be one of the promising strategies to manage CNS disorders. CPPs are short peptide sequences with translocation capacity across the biomembrane. With special regard to their two key advantages like superior permeability as well as low cytotoxicity, these peptide sequences represent an appropriate solution to promote therapeutic/theranostic delivery into the CNS. This scenario highlights CPPs with specific emphasis on their applicability as a novel theranostic delivery system into the brain.

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.

Destructive effect of non-enzymatic glycation on catalase and remediation via curcumin.

Non-enzymatic glycation of proteins is a post-translational modification that is produced by a covalent binding between reducing sugars and amino groups of lysine and arginine residues. In this paper the effect of pathological conditions, derived from hyperglycemia on bovine liver catalase (BLC) as a model protein was considered by measuring enzyme activity, reactive oxygen species (ROS) generation, and changes in catalase conformational properties. We observed that in the presence of glucose, the catalase activity gradually decreased. ROS generation was also involved in the glycation process. Thus, decreased BLC activity was partly considered as a result of ROS generation through glycation. However, in the presence of curcumin the amount of ROS was reduced resulting in increased activity of the glycated catalase. The effect of high glucose level and the potential inhibitory effect of curcumin on aggregation and structural changes of catalase were also investigated. Molecular dynamic simulations also showed that interaction of catalase with curcumin resulted in changes in accessible surface area (ASA) and pKa, two effective parameters of glycation, in potential glycation lysine residues. Thus, the decrease in ASA and increase in pKa of important lysine residues were considered as predominant factors in decreased glycation of BLC by curcumin.

The status of glycation in protein aggregation.

Protein crucial function and flexibility directly depend on its whole structure which is determined by the native distribution of structural elements. Any disturbances in a protein architecture leads to many kind of abnormalities and intra- or extracellular accumulation of misfolded proteins which are the basis of conformational diseases. Glycation is one of the most important unwanted post-translational modifications (PTM) which modifies protein three dimensional decoration and triggers its abnormalities. In current review, we take a look at the brief history of protein glycation, its mechanism and kinetics, glycation consequences and toxic products and its involvement in protein chemical modification, aggregation amyloids and fibril formation and different mechanisms induced by such alterations.