Midtgaardkim3762

The current standard of care of the infection by hepatitis C virus (HCV) is effective in a limited number of patients and the high cost hinders therapy affordability and compliance. In this context, the research of new direct-acting antiviral agents (DAAs) for a more effective and long-lasting therapy is an urgent need and an area of active investigation. In an effort to develop novel DAAs, a series of 1-indanone thiosemicarbazones (TSCs) was synthesized and fully characterized. However, the high self-aggregation tendency and extremely poor aqueous solubility of these antiviral candidates often preclude their reliable biological evaluation in vitro. To maintain constant TSC concentrations over the biological assays, different TSC/cyclodextrin complexes were produced. In the present work, we report for the first time the cytotoxicity and antiviral activity of 5,6-dimethoxy TSC inclusion complexes with hydroxypropyl-β-cyclodextrin on bovine viral diarrhea virus (BVDV) as HCV surrogate model. Results showed a potent suppression of the virus replication, with greater activity for the inclusion complexes than the free compound.It is known that the biological half-life of silver in the central nervous system is longer than in other organs. However, the potential toxicity of silver nanoparticles (NPs) on brain tissue and the underlying mechanism(s) of action are not well understood. In this study, neurotoxicity of silver NPs was examined in rat after intragastric administration. After a two-week exposure to low-dose (1 mg/kg, body weight) or high-dose (10 mg/kg) silver NPs, the pathological and ultrastructural changes in brain tissue were evaluated with H&E staining and transmission electron microscopy. The mRNA expression levels of key tight junction proteins of the blood-brain barrier (BBB) were analyzed by real-time RT-PCR, and several inflammatory factors were assessed in blood using ELISA assay. We observed neuron shrinkage, cytoplasmic or foot swelling of astrocytes, and extra-vascular lymphocytes in silver NP exposure groups. The cadherin 1 (2(-ΔΔCt) 1.45-fold/control) and Claudin-1 (2(-ΔΔCt) 2.77-fold/control) were slightly increase in mRNA expression levels, and IL-4 significantly increased after silver NP exposure. It was suggest that silver NP can induce neuronal degeneration and astrocyte swelling, even with a low-dose (1 mg/kg) oral exposure. One potential mechanism for the effects of silver NPs to the nervous cells is involved in inflammatory effects.This work reports the development of oil in water (o/w) nanoemulsions containing poly(ethylene oxide)-poly(propylene oxide) block copolymer surfactant for the formulation of a delivery system for endovenous zinc and chloroaluminum phthalocyanines. A solubility study suggested clove oil and its combination with ethanol as the best candidates for the oil phase composition. The nanoemulsions were obtained using a high-pressure homogenizer and analyzed for droplet size to determine their short- and long-term stability. Formulations containing 7 and 10% oil phase and 12% surfactant presented higher stability and allowed the incorporation of a bigger amount of phthalocyanines in the formulation. Rheological analyses showed the prevailing Newtonian behavior of the nanoemulsions. Studies of toxicity and phototoxicity determined that the nanoemulsions produced were capable of inhibiting the growth of adenocarcinoma tumor cells. The nanoemulsions proved to be a good alternative for use in photodynamic therapy.In this paper, we have reported the synthesize of CdS Nanoparticles through microemulsion mediated Triton X-100 neutral micelles at room temperature and its anti-biofilm activity against Escherichia coli. The encapsulated micelles nanoparticle system was studied for its absorption at 450 nm and emission spectrum was recorded peaking at 402 and 425 nm excited at 350 nm. The X-ray diffractive pattern (XRD) was confirmed the presence of cubic CdS crystallites. High resolution Transmission electron microscopy (HRTEM) reveals that the particles were spherical in shape and average size is 20 nm. Anti-biofilm activity of CdS nanoparticles were studied at 5 μL and inhibition of growth of biofilm formed by Escherichia coli bacteria was documented by confocal laser scanning microscopy(CLSM) and confirmed that CdS nanoparticles in low concentration have very good anti-biofilm activity and hence may be used in antibacterial drug formulation.Carbonized human hair is used to stop bleeding in traditional Chinese medicine. The present study was aimed to prepare a novel nanofiber containing carbonized human hair and evaluate its hemostatic effect. Carbonized human hair-loaded poly(L-lactic) acid nanofiber was prepared by electrospinning. The hemostatic efficacies of dressings composed of either carbonized human hair, carbonized human hair-loaded poly(L-lactic) acid nanofiber, Yunnan White Drug power or poly(L-lactic) acid nanofiber were investigated in several swine arterial and venous bleeding models. Blood loss and bleeding time were measured. In vitro, carbonized human hair, carbonized human hair-loaded nanofiber and Yunnan White Drug Powder significantly shortened the clotting time in comparison with the nanofiber control group. The hemostatic effects of the carbonized human hair-load nanofiber on liver and spleen traumatic wounds were better than those of carbonized human hair and Yunnan White Drug Powder in terms of blood loss and bleeding time. Similar effects were observed in swine femoral artery wound model. In the swine femoral vein wound model, bleeding could not be stopped in the control animals. In the carbonized human hair group, Yunnan White Drug Powder group and carbonized human hair-load nanofiber group, bleeding was stopped in 83.3%, 83.3% and 100% of the animals, respectively. In conclusion, dressing using carbonized human hair-load nanofibers is effective in controlling severe, uncontrolled bleeding. This dressing may offer a cheap alternative to dressings composed of coagulation proteins.In this study, the bone-like composite membrane based on blends of gelatin (Gel), nano-hydroxyapatite (n-HA) and poly(vinyl alcohol) (PVA) was fabricated by solvent casting and evaporation methods. The effect of n-HA content and the ratio of Gel/PVA on the properties of the composite was investigated. The Gel/PVA and n-HA/Gel/PVA composite membranes were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), water contact angle measurement and scanning electron microscopy (SEM). The mechanical properties of the composites were determined by tensile tests. The as prepared composite membranes exhibited hydrophobility, the water contact angle of composite membrane was 126.6 when its mass ratio of n-HA/Gel/PVA was 10/50/40. The tensile strength of composite membranes was greatly increased due to the introduction of n-HA, and the tensile strength was increased to 74.92 MPa when the mass ratio of n-HA/Gel/PVA was 10/50/40. SEM observation indicated that n-HA was dispersed in the membranes and a sea-island structure was formed in the n-HA/Gel/PVA composite membranes, resulting in a significant increase in tensile strength. The as-prepared n-HA/Gel/PVA composite membranes may be applied in the field of bone tissue engineering.In this investigation, ultrasonication process was used for the synthesis of magnesium doped nano-hydroxyapatite (MH) (0, 1, 2, and 3 mol% of Mg concentration) particles with controlled size and surface morphology. The size of the prepared MH particles was in the range of 20-100 nm with narrow distribution. Increase in the concentration of Mg reduced the particle size distribution from 60 to 40 nm. On incorporation of Mg in HAp lattice, an increase of 20-66 nm in specific surface area was observed in microporous HAp particles. XRF and XRD patterns reveal that the particles possess stoichiometric composition with reduced crystallinity with respect to the Mg concentration. Surface morphology of MH/chitosan (CTS) coated implant was found to be uniform without any defects. The corrosion rate of the implant decreased with increase in Mg concentration. The in vitro formation of bonelike apatite layer on the surface of the MH/CTS coated implant was observed from simulated body fluid studies. The antimicrobial activity of the MH/CTS composites against gram-positive and gram-negative bacterial strains indicated that increasing Mg concentration enhanced antimicrobial properties. Nanoindentation analysis of apatite coated implant surface reveals that the mechanical property depends on the concentration of magnesium in HAp. From the cytotoxicity analysis against NIH 3T3 fibroblast, it was observed that the Mg incorporated HAp/CTS composite was less toxic than the MHO/CTS composite. From this result, it was concluded that the MH/CTS nanocomposites coated implant is the excellent material for implants.Self-assembly of DNA concatemers from native duplexes and those containing non-nucleotidic bridges of varying polarity composed of repeating oligo(ethylene glycol) phosphates -O(CH2CH2O)(n)PO2- or α,Ω-alkanediol phosphates -O(CH2)10OPO2(-)- units was compared. The structures obtained were characterised by polyacrylamide gel electrophoresis, enzymatic digestion and AFM. Our results have revealed that chemically-modified duplexes favour self-termination of concatemer growth and yield up to 35% of nanosized DNA rings.The somatostatin receptors (SR), which are overexpressed in a majority of neuroendocrine tumors, are targets for radiopeptide-based imaging using for example the 99mTc-Tyr3-Octreotide peptide. Dendrimers are hyperbranched polymeric structures. The nanoscopic size and near-monodisperse nature properties give polyamidoamine (PAMAM) dendrimers an edge over linear polymers in the context of drug delivery. Gold nanoparticles (AuNPs) conjugated to peptides produces stable multimeric systems with target-specific molecular recognition. The aim of this research was to prepare two nanosized multimeric systems for neuroendocrine tumor imaging, 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr-Octreotide, and to compare their in vitro uptake in SR-positive AR42J cancer cells as well as their biodistribution profile in athymic mice bearing AR42J tumors. Navitoclax solubility dmso [Tyr3, Lys(Boc)5]-Octreotide was conjugated to the carboxylate groups of the PAMAM dendrimer (G3.5) with further Boc deprotection using TFA. 99mTc labeling was carried out bye conjugate showed a significant renal excretion. Both radiopharmaceuticals demonstrated properties suitable for use as target-specific agents for molecular imaging of tumors that overexpressed SR.Inflammatory and infectious diseases are one of the most common causes of mortality and morbidity. This paper aimed to prepare and to evaluate the ability of long-circulating and pH-sensitive liposomes, trapping a radiotracer, to identify inflamed focus. The physicochemical characterization of freeze-dried liposomes, using glucose as cryoprotectant, showed 80% of the vesicles with adequate mean diameter and good vesicle size homogeneity. Radiotracer encapsulation percentage in liposomes was 10.65%, of which 4.88% was adsorbed on the surface of the vesicles. Furthermore, liposomes presented positive zeta potential. Freeze-dried liposomes, stored for 180 days at 4 degrees C, did not show significant changes in the mean diameter, indicating good stability. Free radiotracer and radiolabeled liposomes were injected into inflammation focus-bearing rats, and ex-vivo biodistribution studies and scintigraphic images were performed. Results showed that radiopharmaceutical, free and encapsulated into liposomes, were able to identify the inflamed site.