سال:1396 | دوره: | شماره: |تعداد مقالات:10

Current licensed and commercially available prophylactic human papillomavirus (HPV) vaccines (Cervarix and quadrivalent/nine valents Gardasil) are based on major capsid protein L1 virus-like particles (VLPs) production which are expensive and type specific. Minor capsid L2-RG1 linear epitope (17-36) is a known candidate for induction of cross-neutralizing antibodies to develop low-cost pan-HPV vaccines. Herein, we report construction and expression of a three tandem repeats of L2-RG1 derived from HPV16 and 18 fused with the same head to tail pattern (HPV16: 17-36×3+HPV18: 17-36×3; hereafter termed dual-type fusion L2 peptide) in E. coli and provide the results of its immunogenicity in mice. SDS-PAGE and western blot analyses indicated proper expression of the peptide that could be further purified by Ni-NTA affinity chromatography via the located C-terminal 6xHis-tag. Mice immunized by formulation of the purified peptide and Freund adjuvant raised neutralizing antibodies which showed proper cross reactivity to HPV L2 (11-200) of types: 18, 16, 31 and 45 (which totally are responsible for 90% of cervical cancers) and efficiently neutralized HPV18/16 pseudovirusesin vitro. Our results imply the possibility of development of a simple, low-cost preventive HPV vaccine based on this dual-type fusion L2 peptide in bacterial expression system with broad spectrum.

Magnetic nanoparticles (MNPs) are of high interest due to their application in medical fields, in particular for theranostics. Specific properties required for such particles include high magnetization, appropriate size and stability. Biocompatible magnetically soft magnetite particles (Fe3O4) have been investigated for biological purposes. The intrinsic instability of these nanoparticles and their susceptibility to the oxidization in air, are limitations for their applications. Various methods have been described for synthesis of these nanoparticles among which co-precipitation method is widely experimented. In order to illustrate the synthesis of MNPs elaborately, the effect of different factors on particle formation were studied. The particles morphology, stability, paramagnetic effect, chemical structure and cytotoxicity were evaluated. Particles of 58 and 60 nm obtained by oleic acid coated (OMNPs) and citric acid coated (CMNPs) magnetite nanoparticles respectively. Transmission electron microscopy images exhibited the real sizes are 15 and 13 nm. Magnetic saturations of these nanoparticles were 72 and 68 emu/g which is suitable for medical applications. Both OMNPs and CMNPs were non-toxic to the SK-Br-3 and MCF-7 cells in the concentrations of<2.5 mg/mL. Since these particles exhibit relatively high magnetic saturation, low dose of such material would be required; therefore, these NPs seem to be suitable for theranostics.

The marine environment covers three quarters of the surface of the planet and is estimated to be home to more than 80% of life but yet it remains largely unexplored. It harbours a number of macro and microorganisms that have developed unique metabolic abilities to ensure their survival in diverse and hostile habitats, resulting in the biosynthesis of an array of secondary metabolites with specific activities. In this study, pigment forming bacterial strains were isolated from the sea surface inter tidal zones at different sampling sites along the Visakhapatnam coastal region. The bacterial isolates showed various types of colour pigments like pink, yellow, orange, and brown. Out of 26 pigmented isolates obtained, the bacterial isolate with bright yellow pigmentation was selected for further study. This strain was identified as Brevibacterium spby using morphological, physiological, biochemical and 16s rRNA sequencing methods. The pigment was extracted in methanol solvent and antibacterial activity of the pigments extracted from the bacteria was determined and it was found active against pathogenic bacteria. The pigment extract was tested In vivo for anti-inflammatory activity and was effective.

Quinazolinones are a group of heterocyclic compounds that have important biological activities such as cytotoxicity, anti-bacterial, and anti-fungal effects. Thiazole-containing compounds have also many biological effects including antitumor, antibacterial, anti-inflammatory, and analgesic activities. Due to significant cytotoxic effects of both quinazoline and thiazole derivatives, in this work a group of quinazolinone-thiazol hybrids were prepared and their cytotoxic effects on three cell lines were evaluated using MTT assay. CompoundsA3, A2, B4, and A1 showed highest cytotoxic activities against PC3 cell line. CompoundsA3, A5, and A2 were most active against MCF-7 and A3, A5, and A6 showed good cytotoxic effect on HT-29 cell line. According to the results, A3 efficiently inhibited all cell growth tested in a dose dependent manner. The IC50 of A3 was 10 M, 10 mM, and 12 mM on PC3, MCF-7, and HT-29 cells, respectively.

Allium affineis a member of Amaryllidaceae family, which grows wildly in some western regions of Iran.Limited information is available about the pharmacological activities of this plant. The present study aimed to evaluate thefibrinolytic and antioxidant effects of hydroalcoholic extract of A. affine aerial parts. The in vitro antioxidant properties of the extract were evaluated by total phenolic content assay, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP) assay. Thein vivo studies included the determination of hydroperoxides level and FRAP value in serum samples of rats receiving i.p. injections of the plant extract for 21 days. The fibrinolytic activity of the extract was quantitatively evaluated by measuring the clot weight. In vitro antioxidant analysis exhibited the promising potential of DPPH scavenging and total antioxidant capacity of A. affine extract. In the in vivo analysis, A. affine extract reduced the serum hydroperoxides level and increased the serum total antioxidant capacity in rats. In vitro fibrinolytic assay also elucidated notable thrombolytic activity of the plant extract. The results of this study revealed the valuable antioxidant and in vitro fibrinolytic activities of A. affine extract. Further studies are needed for better evaluation of anticoagulant and thrombolytic activities of this plant and understanding its detailed mechanisms.

A well-characterized and fully validated ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometric (UHPLC-ESI-MS/MS) method was developed to reliably analyze combination of perindopril arginine and amlodipine besylate in bulk and tablet formulations. The chromatographic separation was achieved on a Waters ACQUITY UPLCÒ BEH C18 column with 1.7 mm particle packing which enabled the higher peak capacity, greater resolution, increased sensitivity, and higher speed of analysis using a volatile mobile phase ideally being at least 2 pH units below and above the perindopril arginine and amlodipine besylate pKa, respectively. Mass spectrometric detection was performed using electrospray ion source in positive ion polarity to profile the abundances of perindopril arginine and amlodipine besylate, using the transitions m/z 369® m/z 172, and m/z 409 ® m/z 238 for perindopril arginine and amlodipine besylate, respectively. Calibration curve was constructed over the range 0.25 – 500 ng/mL and 1.0 – 100 ng/mL for perindopril arginine and amlodipine besylate, respectively. The method was precise and accurate, and provided recovery rates>80% for both compounds. Furthermore, the intra- and inter-assay precision in terms of % RSD was in between 0.1 – 3.7 for both perindopril arginine and amlodipine besylate. A specific, accurate, and precise UHPLC-MS/MS method for the determination of perindopril arginine and amlodipine besylate in bulk and tablet formulation.

The aim of this study was to evaluate the role of inflammation and oxidative damage in hepatotoxicity of ethanol. Also we assessed protective effects of atorvastatin against ethanol-induced hepatotoxicity. In this study, the animals were divided into five groups: control, ethanol (10 mg/kg intraperitoneal (i.p.)), ethanol with atorvastatin (10, 20 mg/kg/day, i.p.) and ethanol-vitamin C group which received ethanol (10 mg/kg/day) plus vitamin C (200 mg/kg, i.p.) for 28 consecutive days. Then, the animals were euthanized and liver tissues were separated. Biochemical markers ALT and AST were measured. Moreover, glutathione (GSH) content, lipid peroxidation, protein carbonyl, nitric oxide and tumor necrosis factor-a (TNF-a) were evaluated. The administration of ethanol for 28 days resulted in an increase in liver damage, oxidative stress and inflammatory markers. The atorvastatin was able to prevent the ethanol-induced hepatotoxicity by decreasing the oxidative stress and inflammation processes. Our study showed the critical role of oxidative damage and inflammation in ethanol-induced hepatotoxicity that markedly was inhibited by administration of atorvastatin. Therefore, atorvastatin can be suggested for prevention of ethanol-induced hepatotoxicity.

Colitis is an inflammatory disease of the intestine with unknown etiology involving multiple immune, genetic, and environmental factors. We were interested to examine the effect of total extract from Dracocephalum Kotschyi (D. kotschyi) Boiss. on the experimental colitis. D. kotschyi hydroalcoholic extract (10, 20, and 40 mg/kg) or apigenin (5, 10, and 20 mg/kg) were administered orally 2 h prior to induction of colitis which was induced by intrarectal administration of acetic acid (4%) in rats. Prednisolone (4 m/kg) was used as the standard drug for comparison. Biochemical evaluation of inflamed colon was performed by measuring myeloperoxidase (MPO) activity. After 5 days treatment, mucosal ulceration was evaluated. Intrarectal instillation of acetic acid caused significant inflammatory reactions as indicated by macroscopic and microscopic changes. The activity of MPO increased in vehicle treated groups while recovered to normal level by pretreatment of animals with D. kotschyi extract, apigenin, or prednisolone. D. kotschyi and apigenin-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared with the vehicle-treated negative control group. The beneficial effect of apigenin was comparable with that of prednisolone. This research has shown the anti-inflammatory potential of D. kotschyiextract and apigenin in experimentally induced colitis.

1, 3, 4-oxadiazoles are interesting compounds because of their valuable biological effects such as cytotoxic, antibacterial, antifungal, and anti-tubercular activities. Ethyl mandelate was treated with hydrazine hydrate to yield the corresponding acylhydrazide. Some of the 2, 5 disubstituted 1, 3, 4-oxadiazole derivatives were prepared from acylhydrazide using three different procedures. In the first procedure, acylhydrazide was reacted with nitro or chloro aroyle chloride to afford a diacylhydrazide which was cyclized to 2, 5-disubstituted 1, 3, 4-oxadiazole in the presence of phosphoryl chloride as dehydrating agent. In the second procedure, furan-oxadiazole derivative was directly prepared from carboxylic acid and acylhydrazide in one step. In the third procedure, acyl hydrazide was condensed with 5-nitrofuraldehyde to yield 5-nitrofuran-2-yl) methylene) -2-phenyl acetohydrazide intermediate which was cyclized to form the nitrofuran-oxadiazole derivative by acetic anhydride as dehydrating agent. The structures of these compounds have been elucidated by spectral IR and 1H-NMR analysis. All the newly synthesized compounds were screened for their antibacterial and antifungal activities. Compounds F3 and F4 showed remarkable antibacterial activities against Staphylococcus aureus and Escherichia coli bacteria.

The anti-inflammatory effects of anti-depressants have been demonstrated recently. Doxepin, a tricyclic antidepressant drug (TCA), has some special properties in comparison with the other members of its family. It has some H1, H2, alpha-1 adrenergic and muscarinic receptor blocking effects. It revealed also anti-nociceptive and relatively potent sedative effects. This study was aimed to evaluate its possible antiinflammatory effect in a well-established animal model. Male Wistar rats weighing 200-250 g were used in carrageenan-induced inflammatory paw edema model. The test and control drugs were injected by intraperitoneal (i. p. ) and intracerebral (i. c. v. ) routes. The anti-inflammatory activity of doxepin (15, 30 and 60 mg/kg, i. p. and 50 and 100 μ g/rat, i. c. v. ) and the reference drug, dexamethasone (2 mg/kg, i. p. ) were evaluated by determination and comparison of some involved biological markers including the paw volume, cytokine levels (interleukin 6 (IL-6), IL-1β , tumor necrosis factor α (TNFα )), myeloperoxidase (MPO) activity and histopathological parameters. All i. p. doses of doxepin showed significant anti-inflammatory effect. It also significantly reduced MPO activity and cytokine levels and improved histopathologic parameters of carrageenan-injected paw tissues. I. c. v. administration of the drug did not show any significant reduction of carrageenan-induced paw edema. Although the exact mechanism of the anti-inflammatory effect of doxepin is not clear, it seems that reduced leukocyte migration and pro-inflammatory cytokines play important role in its anti-inflammatory effect. Also central sites are not involved in the anti-inflammatory effect of the drug.