Structural and Dynamic Insight into Hirudin Epitopes-HLADRB1 0101 Complexes and their Modified Peptide Ligands: A Molecular Dynamic Simulation Study

Purpose: To develop a hirudin therapeutic protein that eliminates unwanted immune response.Methods: Molecular dynamic simulation was performed on immunodominant hirudin epitopes 1-15 and 13-27 and its analog, modified peptide ligands (MPLs), namely, [Lys4] Hir1-15 and [Gly9] Hir1-15, [Gly21] Hir13-27 and [Lys21] Hir13-27. The selected epitopes were modeled and 20 ns of molecular dynamics simulation was performed on peptide-HLA1 0101 and MPLs-HLA1 0101 complexes to gain a better understanding of molecular recognition mechanisms of MHC peptide binding. Characterization of the process was done by evaluation of root mean square deviation (RMSD) and total energy of binding.Result: All complexes of MPLs-HLA-DRB1 0101 showed thermodynamically unstable structure in comparison with native epitopes-HLA-DRB1 0101. The findings indicate that these analogs have different orientation in HLA grooves and are not available for suitable interaction with HLA-DRB1 0101.Conclusion: Altogether, the results show the potentials of predictive methods and molecular modeling in molecular mimicry of peptide-MHC interaction and provide insights into the binding characteristics of antigen presentation mechanism.Keywords: Modified peptide ligand, Epitopes, MHC peptide binding, Hirudin, Modified peptide ligands, Molecular dynamic simulation, Binding free energ

Effect of inulin supplementation in male mice fed with high fat diet on biochemical profile and α-amylase gene expression

Purpose: To evaluate the preventive and therapeutic effects of inulin  supplementation in Naval Medical Research Institute (NMRI) male mice fed with high fat diet.Methods: NMRI male mice (n = 36) were divided into three groups. Control (C1), obese (O1) and experimental mice (E1) were fed during 8 weeks as follows: C1 with normal rodent pellet, O1 with high fat diet, and E1 with high fat diet plus 20 % inulin. C2, O2, and E2 were fed as follows: C2 with normal rodent pellets for 12 weeks; O2 with high fat diet during 8 weeks and switched to normal rodent pellet during next 4 weeks; and E2 with high fat diet over a period of 8 weeks and switched to normal rodent pellet plus 20 % inulin for 4 weeks. Body weight, serum glucose,  triglycerides, total cholesterol, high density lipoprotein (HDL), low density  lipoprotein (LDL), and hepatic α-amylase gene expression were measured.Results: Groups receiving high fat diet showed higher weight (30.71 ± 0.66 g in O2, p < 0.001), nonfasting blood glucose levels (257.69 ± 5.10 mg/dl in O2, p < 0.001), TG (282.15 ± 1.83 mg/dl in O2, (p < 0.001)), and cholesterol levels  (335.72 ± 2.23 mg/dl in O2, (p < 0.001)), compared with control. In C2 group, mean body weight was 25.71 ± 0.54 g, non-fasting blood level 161.54 ± 4.48 mg/dl, TG level 214.29 ± 5.54 mg/dl, and cholesterol level 164.29 ±4.57 mg/dl. Compared to obese group, mice receiving inulin showed lower blood glucose levels (223.10 ± 8.7 mg/dl in E2, p < 0.001), body weight (27.86 ± 0.57 g in E2, p < 0.001), TG (232.14 ± 4.02 mg/dl in E2, p < 0.001) and cholesterol (249.97 ±2.28 in E2, p < 0.001). A slight decrease in hepatic α-amylase gene expression was observed only in E1.Conclusion: Besides its sweetening properties, inulin may also find use as a potential anti-obesity compound.Keywords: High-fat diet, Inulin, Obesity, Blood glucose, Biochemical profil

Benzothiazole Thioflavin T improves obesity-related symptoms in mice

Background and Purposes: In order to counteract the obesity epidemics, novel therapeutics are needed. Thioflavin T (ThT) is a benzothiazole used as an amyloid probe and has other properties such as anti-aging and antihyperglycemic effects. The current study aimed at investigating its effect on obesity. Materials and Methods: A mouse model of obesity was generated by feeding male NMRI mice with a high fat diet (HFD) for 8 weeks. After this period, mice diet was switched to normal rodent diet, and ThT was orally administered with a 12 mg/Kg dose. The treatment effect was assessed on biochemical parameters, adipokines (adiponectin and leptin), total antioxidant capacity and TNF-α. Histological investigation was made on samples taken from adipose tissue and liver. Results and Conclusion: After receiving HFD, mice exhibited significantly increased body weight compared with a control group as well as well as abnormality in biochemical parameters. A significantly effective result was obtained on body weight, blood glucose, cholesterol and ALT serum levels which decreased in the treated group. ThT caused also a significant decrease in leptin levels and TNF-α. Furthermore, the compound led to a reduction in the size of adipose tissue cells, as well as the number of lipid droplets in hepatic tissue. In conclusion, it is suggested that ThT possess an interesting potential for being used as an anti-obesity drug, especially when considering its previously reported effects as potential anti-diabetic and anti-ageing compound

Citral effect in male NMRI mice nonalcoholic steatosis model: assessing biochemical and histological parameters and PPARα gene expression

Citral is a small molecule present in various citrus species, with reported anti-hyperlipidemic and antiinflammation effects. Here, the effect of intraperitoneal (IP) administration of citral is evaluated in a mouse model of non-alcoholic steatosis. Male NMRI mice were divided into the following groups (n = 12): normal control group (NC) receiving a normal diet; high-fat emulsion group (HF) receiving high fat diet for four weeks; positive control group (C+) receiving HF diet for four weeks and then shifted to normal diet with IP-administered silymarin (80 mg/kg) for four weeks; sham group receiving HF diet for four weeks and then shifted to normal diet for four weeks; and EC1, EC2, and EC3 groups receiving HF diet for four weeks and then shifted to normal diet with IP-administered citral doses of 5, 10, and 20 mg/kg, respectively. HF diet resulted in steatohepatitis with impaired lipid profile, high glucose levels and insulin resistance, impaired liver enzymes, antioxidants, adiponectin and leptin levels, decreased PPARα level, and fibrosis in the liver tissue. Upon treatment with citral, improvement in condition was observed in a dose-dependent manner—both at histological level and in the serum of treated animals. and the PPARα level was also increased

A Comparison of Explanation Methods of Encapsulation Efficacy of Hydroquinone in a Liposomal System

     One of the most important parameters describing the liposomal formulation of hydroquinone is encapsulation efficacy. For the efficacy evaluation of hydroquinone trapped in liposomal structure, there is a need to first separate liposome from the matrix surrounding it. There are various separation techniques; however, in this study, the three techniques of centrifuges with and without washing and dialysis were used. From among the laboratory techniques, an appropriate method is the one that offers responses with a high repeatability. The statistical calculations revealed that encapsulation efficacy with a direct method resulted from a separation via the techniques of dialysis and centrifuge without washing had the highest dispersion with SDs of 6.1 and 8.7, respectively, while the SD value in the technique of centrifuge with washing was 5.2. Through an indirect method, hydroquinone encapsulation efficacy showed the best repeatability with SD values of 2.8 and 2.1 by using the two techniques of centrifuge and centrifuge filtration, respectively. It seems that the treatments leading to the dilution of hydroquinone formulation would result in hydroquinone leakage and a reduction of encapsulation efficacy. It seems that measurement of hydroquinone encapsulation efficacy with an indirect method is a better choice; therefore,  a centrifuge technique was utilized to report the mentioned efficacy at a speed of 45000 rcf and duration of 30 min due to having a reasonable price and ease of access.

A Novel Missense Mutation in Oncostatin M Receptor Beta Causing Primary Localized Cutaneous Amyloidosis

Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß). OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine) amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus

Learning and Memory Impairment Induced by Amyloid Beta Peptide and Effects of Thymol on Hippocampal Synaptic Plasticity in Rats Fed a High-Fat Diet That Received Amyloid Beta

Thymol is a natural phenolic compound that is present in various plants; the significant antioxidant activities of Thymol may be helpful in preventing the progress of various oxidative stress-related diseases. Recent studies have confirmed that antioxidant-rich foods play a vital role in the disease prevention of neurodegenerative diseases, including Alzheimer’s disease (AD). We examined the protective and therapeutic effects of Thymol on the Aβ-induced long-term potentiation (LTP) impairments in rats fed a high-fat diet. LTP is a type of synaptic activity that has been thoroughly studied in the hippocampus and is thought to be the neural correlate of learning and memory. If Thymol is protective against AD-related impairments, then natural therapeutic agents based on the structure of Thymol could be used to protect against oxidative stress-related illnesses, such as AD

Inhibition of amyloid fibril formation and cytotoxicity by a chemical analog of Curcumin as a stable inhibitor

In this paper, we endeavor for predicting the performance of quantized compressive sensing under the use of sparse reconstruction estimators. We assume that a high rate vector quantizer is used to encode the noisy compressive sensing measurement vector. Exploiting a block sparse source model, we use Gaussian mixture density for modeling the distribution of the source. This allows us to formulate an optimal rate allocation problem for the vector quantizer. Considering noisy CS quantized measurements, we analyze upper- and lower-bounds on reconstruction error performance guarantee of two estimators - convex relaxation based basis pursuit de-noising estimator and an oracle-assisted least-squares estimator.QC 20130118</p