Current Chemical Biology - Volume 12, Issue 2, 2018

Objective: This study investigated differences in catecholamine levels in individuals with and without sleep bruxism. Methods: A search in the databases PubMed, Cochrane Library, Scopus, Web of Science, LILACS, IADR abstracts, grey literature and in reference lists of included studies was conducted. The search was performed by two researchers, supervised by a librarian. There were no filters and no limits to language or year of publication. Eligibility was based on PECO criteria; which means the studies about children and adults (P) with (E) and without bruxism (C) in which the catecholamine levels (O) in any body fluids, were investigated. The studies were qualitatively assessed through a checklist for evaluating their risk of bias. Data were extracted from all included studies. Results: Initially, 269 articles were identified. After removing duplicates, 175 were read (title/abstract), and of these, nine were retrieved to be read in full. One more article was provided by Pubmed alert, but it was excluded. From those nine articles, three studies with chromatographic analysis of catecholamine in urine were included in the qualitative synthesis. Studies have shown an increased level of catecholamine (epinephrine, norepinephrine, and dopamine) in the urine of individuals with sleep bruxism compared with non-bruxers. However, assessment showed flaws in some methodological aspects such as matching and blinding. Conclusion: There are some methodological flaws in the included studies, thus there is little scientific evidence that adults and children with sleep bruxism have higher catecholamine levels in the urine compared to those without bruxism.

Background: This review describes the use of molecularly imprinted polymers (MIPs) as tailor-made adsorbents for developing micro-solid phase extraction (μ-SPE) procedures when isolating/ assessing organic pollutants, drugs, and bioactive compounds from environmental, food, and clinical/ forensic samples. Objective: Developments in MIP-μ-SPE are focused on synthesizing selective MIPs before preparing micro devices, and also when synthesizing MIPs onto nanoparticles such as magnetite (magnetic MIPs). Conclusion: The current paper also reviews advances in MIPs synthesis onto quantum dots (MIP-QDs) for fluorescenssce sensing of organic compounds, advantages and drawbacks of each methodology, and future expected trends.

Background: Due to increased use of antimicrobials, pathogenic bacteria have pioneered their own intrinsic resistance for antibiotics that raise the demand of inventing new antimicrobial agents. These pathogens possessed a bunch of cell transporters which confers resistance to antimicrobial agents known as efflux pump. Five major classes of efflux pumps are resistance nodulation and cell division (RND), small multidrug resistance (SMR), multidrug and toxin extrusion (MATE), major facilitator superfamily (MFS) and ATP binding cassette (ABC). Objective: The authors reviewed different class of efflux pump inhibitors which includes Lphenylalanyl- L-arginyl-β-naphthylamide (PAβN), arylpiperidines and arypiperazines, nocardamines, arylated benzothiophenes and tiophenes, carbonyl cyanide mchlorophenylhydrazone (CCCP), sodium orthovanadate and phenothiazines based on their substrate specificity. Methods & Result: The authors documented the role of efflux pump inhibitor based on their activity upon specific class of efflux pump. The efflux pump inhibitor hinder the efflux pump activity by binding to the receptor, blocking the transport of the drug molecule, by changing protein structure or by reducing the energy involved into pump function. Conclusion: The structure studies assist to design new drug compound which can efficiently inhibit the efflux pump and provide promising efflux pump inhibitor to cure multidrug resistance caused by the bacterial community. 3D structure of the efflux pump reveals the drug binding site and drug dislodgement site. The efflux pump inhibitor reduces the necessity of discovering novel drug molecules and provides a new way to reutilize existing drug with slight modifications.

Background: 125I-insulin and 125I-IGF-I distribution during internalization is seemingly a key condition that determines hormone functional role in a given organism. Endocytosis course of 125Iinsulin and 125I-IGF-I in isolated chicken hepatocytes occurred in different ways as compared with rat hepatocytes. 125I-insulin and 125I-IGF-I distribution across cell membrane during internalization was different in bird cells. Objective: Analysis of their distribution across the cell membrane in chicken cells. Methods: Hepatocytes were isolated according to Berry and Friend (with modifications). Hormone/ receptor complex internalization course was evaluated in a separate experiment with 125I-insulin or 125I-IGF-I. It included a four steps procedure: cells preincubation with labelled ligands at 6°C, incubation at 12°C and 37°C to activate internalization; two-stage cell washing with another buffer, and lastly, radioactivity was counted stepwise in first and second precipitates. Results: 125I-insulin and 125I-IGF-I distribution across cell membrane during internalization into chicken hepatocytes considerably differed from the same peptides distribution in rat hepatocytes. In chicken hepatocytes, 125I-insulin distribution, temperature dependent in a variable manner, with clear “intracellular” type distribution at 6°C, and stable, resistant to changes in incubation temperature, “membrane” type of 125I-IGF-I distribution were revealed. Conclusions: 125I-insulin and 125I-IGF-I distribution is a specific characteristic of internalization, which is capable of changing, despite retaining basic internalization characteristics of both insulin and IGF-I in the cells of different animal species. The differences of 125I-insulin and 125I-IGF-I distribution types in chicken and rat cells, allow us to guess correctly other functional roles of insulin and IGF-I in birds as compared with mammals.

Background: Enzyme ITPA participates in purine metabolism and its deficiency plays a role in several human diseases. There is growing evidence that ITPA polymorphism is also an important pharmacogenic phenotype, leading to a change in sensitivity to several drugs. ITPA deficiency exists in humans and is observed as elevated levels of ITP. Objective: Allele P32T-ITPA has more pronounced effects but the mechanism of enzyme inactivation is not known. Based on crystallographic data, it was assumed that the mutant loop containing P32T substitution led to uncovering of a hydrophobic residue (Phe31) that served as a marker for enzyme degradation. Method: As the crystal structure of the enzyme may differ from the native structure in a solution, we tested this hypothesis using computer modeling. We simulated the structures of the wild-type homodimer and mutant homo- and heterodimers of the ITPA protein and analyzed these models at small time steps for detecting short-term effects of the conformations of the ITPA enzyme. Results: Comparison of mutant structures with the wild-type structure revealed that the differences were more pronounced for the mutant homodimer than for the heterodimer. There were two regions of strong distinctions – loops between α1-β2 and β5-β6. Two neighboring hydrophobic amino acids (Phe31 and Pro32) were changed by hydrophilic amino acids (Thr32 and Cys33) in the first loop (res. 28-33) due to mutation Phe31-Рro32Тhr-Cys33. The model structure differs from the crystal structure of P32T-ITPA. The position of Phe31 in modeled mutant chains was inward-directed as compared to outward-directed in the crystal and did not serve as a signal for degradation as was predicted. Conclusion: Further investigations are needed for understanding the mechanism of enzyme inactivation by P32T substitution in ITPA.

Background: The objective of the present study is to determine and compare TAS (Total Antioxidant Status), TOS (Total Oxidant Status) and OSI (Oxidative Stress Index) and heavy metal content (Fe, Zn, Cu, Pb and Ni) in Pholiota limonella (Peck) Sacc. mushroom samples collected from Balikesir (Kaz Mountain National Park) and Yalova (Cinarcik, Hasan Baba Picnic Area) provinces. Methods: Mushroom TAS, TOS and OSI values were determined using Rel Assay Diagnostics kits. Heavy metal content was determined using an atomic absorption spectrophotometer. Results: As a result of the studies, TAS values in the samples collected from Balikesir and Yalova were; 2.378 and 2.263 mmol, respectively; TOS values were, 4.742 and 33.022 μmol; while OSI valueswere determined to be 0.199 and 1.459,respectively. Fe, Zn, Cu, Pb and Ni contents were found to be 31.41, 7.13, 2.45, 3.97 and 0.49, respectively, from Balikesir and 361.50, 46.64, 11.93, 10.58 and 1.02, respectively, from Yalova. Conclusion: Study findings demonstrated that the samples collected at Yalova province had higher heavy metal content and OSI value. As a result, the samples collected from Balikesir (Kaz Mountain National Park) were concluded to be healthier.

Background: There are complex methods to induce type 2 diabetes as multiple low-doses streptozotocin with high fat diet administration and other combined methods which induce modest DNA damage, leading to the incomplete destruction of β cells for insulin-resistant diabetes in mice. Objective: An innovative and simple protocol was investigated to induce type 2 diabetes by only Incremental Multiple Low-Doses Streptozotocin (IMLDS) in mice. The effects of hydrocortisone injection on diabetes induction and pancreatic β-cells signaling were also surveyed. Methods: IMLDS designed protocol was conducted in 4 consecutive days by streptozotocin injections of 20, 40, 80 and 160 mg/kg BW/day and stress induced by hydrocortisone injections of 5, 10 and 20 mg/kg BW/day in mice, respectively. The glucose, insulin, glucagon-like peptide 1, RAC-beta serine/ threonine-protein kinase and dipeptidyl peptidase IV of blood were assessed by ELISA. Results: The glucose, glucagon-like peptide 1, RAC-beta serine/threonine-protein kinase levels, and food and water intake increased (p<0.01) while serum dipeptidyl peptidase IV activity decreased (p<0.01) after the administration of novel protocol. Daily injections of hydrocortisone raised blood glucose, glucagon-like peptide 1 and RAC-beta serine/threonine-protein kinase and reduced serum insulin and dipeptidyl peptidase IV activity (p<0.05). By executing this protocol, the serum insulin increased, whereas hydrocortisone injection caused reduction in the insulin (p<0.05). The hydrocortisone administration reduced glucagon-like peptide 1 in the non-induction of IMLDS conditions, but hydrocortisone enhanced glucagon-like peptide 1 after IMLDS (p<0.05). Conclusion: This new protocol may provide a practical and unique alternative chemical protocol for the induction of insulin resistance diabetes (type 2 diabetes) in mice. Stress induced by hydrocortisone also intensifies type 2 diabetes in this animal model.

Background: Alzheimer's disease (AD) is the fourth largest cause of death among people over 65 years of age. Accumulation of β-amyloid and cholinergic deficiency are two prominent pathological descriptions for AD. Objective: Depletion of acetylcholine at the site of its action is thought to be the prime cause of AD. It has been reported that tetrahydrocannabinol (THC) exhibits anticholinesterase activity and it has been proposed as a suitable candidate for treating neurological disorders such as AD. Methods: Using an in silico approach, including virtual screening, THC and its derivatives were docked against acetylcholine binding protein (AChBP) using AutoDock. The top-ranked molecules were studied in detail using an induced fit docking approach followed by characterization of their binding affinity, toxicity and ADME properties using TOPKAT and QikProp. Results: THC_JUIT25, a novel derivative of THC, showed maximum binding affinity and was observed as a promising candidate for performing receptor-ligand interaction studies using molecular dynamics simulation. Conclusion: In this study, we propose a novel THC derivative as a potential lead molecule in the drug development strategy for treating AD.

Background: The occurrence of Parkinson's Disease (PD) is associated with the deposition of proteinaceous aggregates formed by the self-assembly of α-synuclein protein. The pathogenesis of PD has been reported to be linked with the α-synuclein gene. However, the presence of missense mutations: A30P, A53T, E46K, H50Q, G51D and A53E has also been linked with the autosomal inheritance of PD. Recently, it has been highlighted that C-terminal truncated α-synucleins undergo aggregation at a faster rate while the full-length α-synucleins are critical. Objective: To study the dimerization of C-terminal truncations of α-synuclein and its effect on the aggregation propensity. Methodology: We investigated the dimerization of the two important C-terminal truncations (120 and 123) of α-synuclein using Molecular Dynamics Simulation and Potential of Mean Force (PMF) study. Results: From our PMF study, we observed that the binding free energy value to be larger for the association of C-terminal truncated α-synucleins than the value that has been reported for Wild-Type (WT) in our earlier study. Conclusion: Truncating the C-terminal region (which is considered to be intra-molecular chaperone) in α-synucleins exposes the hydrophobic region and thereby increases the aggregation propensity.