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Background: Current medications especially the pentavalent antimonial compounds have been used as the first line treatment of cutaneous leishmaniasis (CL), but they have limitations due to serious side effects such as drug resistance, cardio and nephrotoxicity, and high costs. Hence, the demand to find more usable drugs is evident. Synthesis and development of natural, effective, biocompatible, and harmless compounds against Leishmania major is the principal priority of this study. Methods: By electrospinning method, a new type of nanofiber were synthesized from royal jelly and propolis with different ratios. Nanofibers were characterized by Scanning Electron Microscope (SEM), Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA), Contact angle, and Fourier-transform infrared spectroscopy (FTIR). The Half-maximal inhibitory concentration (IC50), Half-maximal effective concentration (EC50) and the 50% cytotoxic concentration (CC50) for different concentrations of nanofibers were determined using quantitative calorimetric methods. Inductively coupled plasma-optical emission spectrometry (ICP-OES) and flow cytometry were performed as complementary tests. Results: The results showed that the proposed formulas provide a new achievement that, despite the significant killing activity on L. major, has negligible cytotoxicity on the host cells. Royal jelly nanofibers have significantly shown the best 72 hours results (IC50= 35 μg/ml and EC50=16.4 μg/ml) and the least cytotoxicity. Conclusion: This study presents a great challenge to introduce a new low-cost treatment method for CL, accelerate wound healing, and reduce scarring with minimal side effects and biocompatible materials. Royal jelly and propolis nanofibers significantly inhibit the growth of L. major in-vitro. [ABSTRACT FROM AUTHOR]

Background & Objective: Epstein-Barr virus nuclear antigen-1 (EBNA1) is one of the most important proteins of Epstein-Barr virus (EBV) that might be mutated in various related cancers. The purpose of this study was to compare EBNA1 mutations in the C-terminal region between patients with cervical and ovarian cancer and healthy individuals. Methods: As test and control groups, 18 EBV-positive paraffin-embedded samples of cervical and ovarian cancer and 10 age- and gender-matched healthy volunteers who did not have cancer but were EBV-positive were both used. Utilizing a commercial DNA extraction kit, total DNA was extracted following deparaffinization. The entire C-terminal region of the EBNA1 sequence was amplified using an in-house nested PCR. Phylogenetic analysis and Sanger sequencing were used to analyze the sequences using MEGA 7 software and through NJ method. Results: Sequence analysis revealed that the P-Ala subtype of EBNA1 was present in all samples. In two and one samples, respectively, of cervical cancer patients, the mutations A1887G and G1891A were found. The G1595T mutation was also detected in four sequences taken from ovarian cancer patients. No statistically significant difference could be found between the frequency of mutations in patients and controls (P>0.05). No known amino acid substitutions were found in the USP7-binding region and the DBD/DD domain. Conclusion: The findings showed that P-Ala is the predominant EBV subtype across all samples. Additionally, as the sequence of EBNA1's C-terminal region is so stable, it's possible that it had little impact on the pathogenesis of ovarian and cervical malignancies. It is advised to conduct additional research to verify these findings. [ABSTRACT FROM AUTHOR]

Background: The use of venom fractions from the Iranian cobra could be useful adjunct treatments of malaria with chloroquine. A metabolomic investigation with 1HNMR spectroscopy was conducted on an effective fraction tested earlier using Plasmodiumberghei as an experimental murine model. Purpose: We sought to ascertain both safety and anti-parasitic effects of experimental therapies. Methods: After purification of the venom fractions, 25 mice were infected, then treated for 4 days with 0.2 ml of 5 mg/kg, 2.5 mg/kg and 1 mg/kg of the effective fraction, chloroquine, and a drug vehicle. An ED50 was obtained using Giemsa staining and real-time PCR analysis. The toxicity tests inspecting both liver and kidney tissues were performed. Results: A clear inhibitory effect on parasitaemia was observed (with 75% inhibition with 5 mg/kg and 50% reduction when 2.5 mg/kg dosage used). ED50 obtained 2.5 mg/kg. The metabolomics were identified as differentiation of aminoacyl-t-RNA biosynthesis, valine, leucine, isoleucine biosynthesis and degradation pathways were observed. Conclusion: Upon therapeutic effects of cobra venom fraction, further optimization of dose-dependent response of pharmacokinetics would be worthwhile for further exploration in adjunct experimental venom therapies. [ABSTRACT FROM AUTHOR]

Objective(s): Malaria is an important parasitic disease with high morbidity and mortality in tropical areas. Resistance to most antimalarial drugs has encouraged the development of new drugs including natural products. Venom is a complex mixture of active pharmaceutical ingredients. The purpose of this study was to investigate the antimalarial activity of purified fractions of Naja naja oxiana. Materials and Methods: Lyophilized venom was purified with a Sephacryl S-200 HR column and the fractions lyophilized and inhibitory concentration 50% against Plasmodium falciparum 3D7 in vitro obtained. The 4th fraction was run on a Mono Q column, and activity against P. falciparum was detected by lactate dehydrogenase assay and purity by SDS PAGE. Large scale culture of the parasite was carried out with and without the active fraction on the ring stage for 48 hr. The parasites were collected and lyophilized and analyzed by 1HNMR. Chemometrics studies were performed using MATLAB, differentiating metabolites were identified by Human Metabolic Database, and metabolic pathways by the Metaboanalyst online package. Results: The active fraction from the ion exchange column had a 50% inhibitory concentration of 0.026 µg/ml on P. falciparum in vitro (P<0.001) with molecular weight of 63 kDa by SDS-PAGE and no hemolytic activity. Metabolomics studies on the two groups with and without the fraction identified 5 differentiating metabolites and a number of related pathways. Conclusion: The metabolites were succinic acid, l-glutamic acid, pyruvic acid, cholesterol, and NAD. The changes in the Krebs cycle and metabolism pathways of nicotinamide and pyruvate were noticeable. [ABSTRACT FROM AUTHOR]