Search

Synthesis and investigation of biological activity of Peganum harmala smoke-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Peganum harmala smoke-loaded PLGA nanoparticles (PHSE-PNP) wer...

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid (M2000) have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of urea, creatinine, GGT, and non-significant changes in uric acid and anti-Phospholipids levels, besides a significant rise in vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

Purpose: Breast cancer is one of the most common cancer among. Chemotherapy and radiation along with surgery are common methods for treating cancer, but they exhibit side effects on normal cells in the body. We used peptides, as new anti-cancer agents, seem to have fewer reactions on the body's natural cells and are specialized markers for targeting cancer cells. Materials and methods: Metabolomics data are obtained by 1HNMR, LC/MS and GC/MS spectrometry and analyzed by chemometrics techniques and the affected metabolic cycles identified using different databases. ZR-75-1 cells were collected with estradiol (positive control), without estradiol (negative control) and estradiol with peptide (treatment group) and the metabolites of these 3 groups were collected by chloroform/methanol or water extraction method. Spectra were analyzed by 1HNMR and chemometric methods using PLS-DA techniques by which differentiating chemical shifts and their respective metabolites were identified using the Human Metabolome Database. The differentiating metabolic pathways were detected using Metaboanalyst.ca website. Results: A concentration of 10-9 M estradiol induced the growth of estradiol-dependent ZR-75-1 cells compared to the control group. A concentration of 10-10 M MH-I peptide inhibited the growth of estradiol-induced growth in this ER + breast cancer cell line. Altered metabolites and metabolic pathway were distinguished. Conclusion: Changes were observed in different amino acids and carbohydrates. The pathways of aminoacyl-t-RNA, glycolysis. Gluconeogenesis and biosynthesis of biotin and amino acids showed the most changes. The results from this study introduces a new peptide drug lead for the treatment of breast cancer with estrogen positive receptor.

Beta 2 glycoprotein I (β2GPI) is a major antigen for autoantibodies present in antiphospholipid antibody syndrome (APS). β2GPI is a single polypeptide with five repeated domains and different conformations. The activated J-shaped conformation of β2GPI binds to negatively charged phospholipids in the membrane via the fifth domain and causes blood clotting reactions. We applied a drug repurposing strategy using virtual screening and molecular dynamics to find the best FDA drugs against the fifth domain of β2GPI. In the first phase, FDA drugs that had the most favorable ΔG with the fifth domain of β2GPI were selected by virtual screening. Among these drugs that had the most favorable ΔG, Vorapaxar and Antrafenine were selected for molecular dynamics (MD) simulation studies. MD simulation was performed to evaluate the stability of Vorapaxar and Antrafenine complexes and the effect of the two drugs on protein conformation. Also, MD simulation was done to investigate the effect of Antrafenine and Vorapaxar on the binding of β2GPI to the platelet model membrane. According to the results, Vorapaxar and Antrafenine were bound to the protein with the favorable binding energy (Vorapaxar and Antrafenine binding energies are - 49.641 and - 38.803 kcal/mol, respectively). In this study, it was shown that unlike protein alone and protein in the Antrafenine complex, the protein in the Vorapaxar complex was completely separated from the model membrane after 350 ns. Moreover, Vorapaxar led to more changes in the activated J-shape of β2GPI. Thus, Vorapaxar can be a suitable candidate for further investigations on the treatment of APS.

Recurrent implantation failure (RIF) refers to cases in which women have had the failure of the embryo implantation after several in vitro fertilization (IVF). The success rate for IVF depends on many different factors. Implantation is a complex step in a successful pregnancy. Antiphospholipid antibodies (aPLs) and platelet-activating factor (PAF) can be considered as effective factors in the embryo implantation. The first purpose of this study is to compare the levels of aPLs and PAF among RIF and fertile control women. The second purpose is evaluating correlations between the blood levels of these factors in this two groups. The levels of twelve types of aPL and PAF in peripheral blood samples of RIF and fertile control women were checked with ELISA method. The results showed that levels of Anti Cardiolipin antibody IgG was above the normal level in 3% of RIF patients. This study examined for the first time the correlation between twelve types of aPLs and PAF in RIF and fertile women. The results of these correlations show that the serum levels of aPLs affects themselves and the serum levels of PAF. The correlation of aPLs levels and PAF levels was different in the two groups. Differences in the correlations of aPLs levels and PAF levels in two groups show that the equal changes in the level of variables examined can have different effects in RIF and the fertile control groups. It is suggested that the correlation between these variables be evaluated in other studies.

Background: Helicobacter pylori (H. pylori) plays the primary role in increasing oxidative stress and causing stomach inflammation, peptic ulcers, and gastric malignancy in the infected patients. L-arginine (Arg) has antibacterial and anti-inflammatory effects. Objectives: The current study aimed at investigating the beneficial effects of L-arginine on inflammation and oxidative stress in patients infected with H. pylori with dyspeptic symptoms. Methods: The current randomized, double-blind controlled, clinical trial was conducted on 34 patients with H. pylori infection referred to the center of digestive disorders affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, in order to undergo endoscopy from December 2016 to September 2017. Patients were classified into two groups (control and treatment); the control group only received triple-drug therapy (including Amoxicillin, Clarithromycin, and Omeprazole), and the treatment group received standard triple-drug therapy and L-Arg capsules for three weeks. Gastric biopsies and serum samples were taken from all patients before and after the study. H. pylori infection was examined by a rapid urease test and antioxidant indices including superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant capacity (TAC) were evaluated in gastric biopsies. In addition, serum samples were used to measure the inflammation factors including interleukin (IL)-8 and tumor necrosis factor (TNF)-α. Results: Level of SOD activity increased significantly in the treatment group compared with that of the control group (4.91 ± 95.21 vs. 4.0 ± 44.11 IU/mg) (P = 0.001). In the treatment group, compared with the control group, the level of TAC increased significantly (0.35 ± 0.60 vs. 0.30 ± 0.9 mM/L) (P = 0.006) and the level of GPX activity increased significantly in the treatment group compared with the control group (10.68 ± 2.39 vs. 5.16 ± 2.12 IU/mg) (P = 0.000). Regarding the inflammation factor, IL-8 decreased significantly in the treatment group compared with the control group (8.00 ± 1.94 vs. 10.28 ± 2.10 pg/mL) (P = 0.002); also TNF-α decreased significantly in the treatment group compared with the control group (9.71 ± 2.69 vs. 12.24 ± 3.29 pg/mL) (P = 0.036), while there was no significant difference in high sensitivity C-reactive protein (hs-CRP) decrease between the treatment and the control groups (2.34 ± 1.28 vs. 3.04 ± 1.58 mg/L) (P = 0.16). Conclusions: Consumption of L-arginine increased antioxidant indices and decreased inflammation in patients infected with H. pylori.