ARA 290, an 11-amino acid linear nonhematopoietic peptide derived from the three-dimensional structure of helix B of the erythropoietin (EPO), interacts selectively with the innate repair receptor (IRR) that arbitrates tissue protection. The aim of this study was to investigate the protective effects of ARA290 against cisplatin-induced nephrotoxicity. For this purpose, HEK-293 and ACHN cells were treated with ARA290 (50–400 nM) and cisplatin (2.5 μM) in pretreatment condition. Then, cytotoxicity, genotoxicity, oxidative stress parameters (ROS, GPx, SOD, and MDA), and inflammatory markers (TNFα, IL6, and IL1β) were evaluated. Furthermore, apoptotic cell death was assessed via caspase-3 activity and tunnel assay. To determine the molecular mechanisms of the possible nephroprotective effects of ARA290, gene and protein expressions of TNFα, IL1β, IL6, Caspase-3, Bax, and Bcl2 were evaluated by real-time PCR and western blot assay, respectively. The findings indicated that ARA290 significantly reduced the DNA damage parameters of comet assay and the frequency of micronuclei induced by cisplatin. Besides, ARA290 improved cisplatin-induced oxidative stress by reducing MDA/ROS levels and enhancing antioxidant enzyme levels. In addition, reduced levels of pro-inflammatory cytokines indicated that cisplatin-induced renal inflammation was mitigated upon the treatment with ARA290. Besides, ARA290 ameliorates cisplatin-induced cell injury by antagonizing apoptosis. Furthermore, the molecular findings indicated that gene and protein levels of TNFα, IL1β, IL6, Caspase-3, and Bax were significantly decreased and gene and protein levels of Bcl2 significantly increased in the ARA290 plus cisplatin group compared with the cisplatin group. These findings revealed that ARA290 as a potent chemo-preventive agent exerted a protective effect on cisplatin-induced nephrotoxicity mostly through its anti-apoptotic, anti-inflammatory, and antioxidant potentials and also suggested that ARA290 might be a new therapeutic approach for patients with acute kidney injury.
The assessment of drug delivery performance of fabricated pristine XC3 monolayers (X = B, N) for the hydroxyurea anticancer drug was performed using periodic DFT calculations. The most stable direction for the adsorption of hydroxyurea drug over the XC3 monolayers was considered and adsorption energies were computed. The adsorption of hydroxyurea on the XC3 monolayers highly depends on the elemental group of X. The BC3 monolayer has stronger adsorption of hydroxyurea drug than the NC3 monolayer. Since pH around malignancy cells is lower than normal cells, we researched drug release around the cancerous cells upon protonation. The solvent energy and adsorption energies obtained for the BC3 monolayer in an aqueous solution are more vital than the NC3 monolayer. The capability of an XC3 monolayer as a vehicle for hydroxyurea drug to treat malignant growth affirmed.
Periodic density functional theory calculations were employed to scrutinize the desired covalent triazine framework interaction with NO, NO2, and HO2 radicals. The band gap in the most stable complexes decreases remarkably following NO > HO2 > NO2. These significant changes in the band gap of the desired covalent triazine framework led to a considerable difference in the system's conductivity after complex formation. These significant variations in the band gap energy and conductivity of the monolayer reveal that the covalent triazine framework of the present study might be a potential sensing medium for detecting the considered radicals.
The remarkable properties of pristine B3O3 nanosheet as a nanocarrier for adsorption and desorption of TEPA anticancer drug for designing potential drug delivery platform were investigated using periodic DFT calculations. We studied the adsorption energy of all stable complexes formed between the drug molecule and B3O3 in gas and aqueous phases along with electronic structure analysis of complexes. Different adsorption configurations were studied for drug/B3O3 complexes, including the interaction of the C atom of the triangular ring, O atom in the TEPA drug with the B atom in B3O3, and indirect drug interaction the middle of the R1 ring cavity of the B3O3 nanosheet. The take-up of TEPA prompts a substantial change of 68.13% in the band gap (Eg) of the B3O3 nanosheet in the most stable complex. The present study results affirmed the application of B3O3 nanosheet as a potential vehicle for TEPA drugs in the treatment of cancerous tissues.
Hormones and their derivatives are widely used to treat different types of diseases such as prostate cancer which is treated by agonists of gonadotropin-releasing hormone. Triptoreline salts are the first therapeutics of this group launched into the market in the form of microparticles (microspheres). Implants, as one of attractive injectable dosage forms, have many advantages over multi-particulate systems. Some of these advantages are dose adjustability, drug absorption improvement, constant release profile, etc. In this research, a new composite of poly-lactic-co-glycolic acid and hyaluronic acid was designed and prepared in the form of implants containing triptorelin acetate for administration as an injection under the skin(subcutaneously) in arm or thigh area. The manufactured implants characterized by Fourier transform infrared spectroscopy, thermas gravimetric analysis, X-ray diffraction and scanning electron microscopy to assess different aspects of structure and morphology. The drug release profile was assessed by high performance liquid chromatography. These characterizations confirmed that the newly designed drug delivery has a good stability during manufacturing process. The release pattern of the implant was also studied and revealed that the release of the model drug follows a zero-order and erosion mechanism. The compatibility between the components of the newly designed implants and the release profile of the delivery system make it a promising device for drug delivery.
s: In this research the ethanol extract of black tea and its tannin free fraction used for green synthesis of gold nanoparticles. All the extracts were used separately for the synthesis of gold nanoparticles through the reduction of aqueous AuCl4¯. Transmission electron microscopy and visible absorption spectroscopy confirmed the reduction of gold ions to gold nanoparticles. The ethanol extract of black tea and its tannin free ethanol extract produced gold nanoparticles in the size ranges of 2.5-27.5 nm and 1.25-17.5 nm with an average size of 10 nm and 3 nm, respectively. The prepared colloid gold nanoparticles, using the ethanol extract of black tea, did not show the appropriate stability during storage time (24 hours) at 4 oC. In contrast, gold colloids, which were synthesized by a tannin free fraction showed no particle aggregation during short and long storage times at the same conditions. To the best of our knowledge, this is the first report on the rapid synthesis of gold nanoparticles using ethanol extract of black tea and its tannin free fraction.
Development of nontoxic, clean techniques for the synthesis of metal nanoparticles such as gold has attracted increasing attention in recent years. Although many reports have been published about the biogenesis of gold nanoparticles using several plant extracts such as Neem leaf broth (Azadirachta indica), the capacity of a large number of such extracts to form gold nanoparticles has yet to be elucidated. In this research a titrimetric assay was employed for preliminary evaluation of the reducing potential of different medicinal plant extracts. All the extracts were used separately for the synthesis of gold nanoparticles through the reduction of aqueous AuCl4 −. After the screening step, the methanol extracts of Eucalyptus camaldulensis and Pelargonium roseum were selected for further studies. The reducing ability of these extracts was significantly enhanced as compared to Neem leaf broth (Azadirachta indica) which was used as control sample. Transmission electron microscopy, energy-dispersive spectroscopy and visible absorption spectroscopy confirmed the reduction of gold ions to gold nanoparticles. The E. camaldulensis and P. roseum extracts produced gold nanoparticles in the size ranges of 1.25 - 17.5 and 2.5 - 27.5 nm with an average size of 5.5 and 7.5 nm, respectively.