Importance of the inter-electrode distance for the electrochemical synthesis of magnetite nanoparticles: Synthesis, characterization, computational modelling, and cytotoxicity

Magnetite (Fe3O4) nanoparticles, are promising inorganic nanomaterials for future biomedical applications due to their low toxicity and unique magnetic properties. However, the synthesis of these particles can often be expensive, energy intensive, and non-scalable, requiring the addition of surfactants to stabilize the material to control the particle size and avoid agglomeration. We wish to report a simple, green, surfactant-free electrochemical synthesis of these materials using a closed aqueous system at ambient temperature. Particle diameter, between 19 and 33 nm, was controlled by simply modifying the distance between the electrodes. These magnetite nanoparticles were then fully characterized using both spectroscopy and microscopy. Vibrational magnetometry indicates that as the size of the particle decreases, the magnetic hysteretic gap decreases, although for samples below 25 nm no inter-sample difference was observed. To support this experimental data, we carried out a Density Functional Theory (DFT) analysis of magnetite containing more than three iron atoms in the cluster, an essential proposition as magnetite contains three distinct iron species. These calculations were used to support the experimental observations, and closely reproduced both the experimental IR spectrum, and the XRD pattern. In vitro cytotoxicity assays showed dose responsive behavior for the nanoparticles, and demonstrated that they are non-Toxic at clinically relevant concentrations; below 200g/mL we observed no toxicity in a 48-hour standard assay. This work represents the first DFT based simulation of this detailed magnetite cluster, and demonstrates that this sustainable synthetic method is capable of producing nanomaterials with a physical and biological profile that might make them suitable for biomedical applications

Molecular beacon strategies for sensing purpose

The improvement of nucleic acid probes as vital molecular engineering devices will cause a noteworthy contribution to developments in bioimaging, biosensing, and disorders diagnosis. The molecular beacon (MB) which was designed by Tyagi and Kramer in 1996, are loop-stem hairpin-designed oligonucleotides armed with a quencher and a dye (also named reporter groups) at the 30 or 50 ends. This construction allows that MBs in the absence of their target complementary molecules do not fluoresce. Through hybridization with their specific targets a spontaneous configuration change on MBs occur and the dye and quencher separate from each other, resulting in emitting the fluorescence. MBs are effective probes for biosensing because of their extraordinary target-specificity, unique structure, inherent fluorescent signal transduction mechanism, low background fluorescence emission, recognition without separation, and favorable thermodynamic properties. In comparison to other probes (such as linear DNA sequences), MBs with the same number of complementary nucleotides matching their target, are multitasking probes. They have advantages of thermodynamic and photostability, flexible ability for conjugation, higher efficient intrinsic signal switching, and ultra-sensitivity. MBs not only are useful for identifying a nucleic acid target but can also be employed for recognition of various non-nucleic acid goals, including heavy metals and cations, enzymes, cells, ATP, etc. Hence, this review highlights the potential of MBs in the improvement of biosensors and their usage in detection of different analytes such as miRNA, mRNA, cocaine, methamphetamine, actin, thrombin, heavy metal and cations and so on. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

Behavioural and molecular study of the effects of rosuvastatin on acquisition and retention of spatial memory impaired by H-89 in rats

There is controversy on the effect of statins on cognitive functions such as spatial memory. In the present study, effect of ten- day oral gavage of rosuvastatin (Ros, 20 mg/kg) on spatial learning and spatial memory retention impaired by H-89, was investigated in male rats. This study was comprised of two sets of experiments each including the following 3 groups (n = 8): Control group treated with DMSO; H-89 group received bilateral intra-hippocampal H-89 (10 μM/side, in DMSO) and Ros- H-89 group orally treated with Ros (20 mg/kg) and H-89 (similar to the H-89 group). For spatial learning (acquisition phase) assessment, from day 7 of Ros gavage, rats were trained in the Morris water maze (MWM) for four days (one block of 4 stages each day) and received daily H-89, 30 min after Ros gavage. On day 11, the probe test was performed. Also, to assess spatial memory retention, from day 7 to 10 of Ros gavage, rats were trained in MWM but received H-89 on day 10 only. On day 12, the probe test was performed. Besides, CREB and p-CREB protein expression was assessed in hippocampal samples and oxidative stress status was assessed in serum samples. We observed that H-89 led to a clear impairment of the spatial learning and spatial memory recall, increased levels of lipid peroxidation and downregulated CREB and p-CREB proteins, compared to the control group. However, Ros prevented H-89-induced deleterious consequences which might be probably in part due to its ameliorative effects on lipid peroxidation index and CREB and p-CREB expression

Effects of berberine on acquisition and reinstatement of morphine-induced conditioned place preference in mice

Objective: It has been shown that berberine, a major component of Berberis vulgaris extract, modulates the activity of several neurotransmitter systems including dopamine (Da) and N-methyl-D-aspartate (NMDA) contributing to rewarding and reinforcing effects of morphine. Drug craving and relapsing even after a long time of abstinence therapy are the most important problems of addiction. In the present study, we investigated the alleviating effects of berberine on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in mice. Materials and Methods: In male NMRI mice, the acquisition of CPP was established by 40 mg/kg of morphine sulphate injection and extinguished after the extinction training and reinstated by a 10 mg/kg injection of morphine.  The effects of different doses of berberine (5, 10, and 20 mg/kg) on the acquisition and reinstatement induced by morphine were evaluated in a conditioned place preference test. Results: The results showed that intraperitoneal administration of berberine (5, 10, and 20 mg/kg) did not induce conditioned appetitive or aversive effects. Injection of berberine (10 and 20 mg/kg) 2 h before the morphine administration reduced acquisition of morphine-induced CPP. In addition, same doses of berberine significantly prevented the reinstatement of morphine-induced CPP. Conclusion: These results suggest that berberine can reduce the acquisition and reinstatement of morphine-induced conditioned place preference and may be useful in treatment of morphine addiction

Effects of silymarin on neuropathic pain and formalin-induced nociception in mice

Objective(s):Based on the previous reports, silymarin can suppress nitric oxide, prostaglandin E2 (PGE2), leukotrienes, cytokines production, and neutrophils infiltration. Regarding the fact that inflammation plays an important role in neuropathic and formalin-induced pain, it was assumed that silymarin could reduce pain. The present study investigates the analgesic effects of silymarin in chemical nociception and a model of neuropathic pain. Materials and Methods: Chemical nociception was produced by injection of 20 µl of formalin (0.5% formaldehyde in saline) into the plantar region of the right hind paw. A sciatic-nerve ligated mouse was applied as the model of neuropathic pain and the antinociceptive response of silymarin was examined 14 days after unilateral nerve-ligation using the hot plate test. Results:The intraperitoneal administration of silymarin (25, 50, and, 100 mg/kg) 2 hr prior to the intraplantar formalin injection suppressed the nociceptive response during the late phase of the formalin test significantly, but it was not in a dose-dependent manner. Different doses of silymarin 14 days after unilateral sciatic nerve ligation in hot plate test did not induce obvious antinociception. Conclusion:Results of the present study indicated that repeated administration of silymarin prevents the formalin-induced nociceptive behavior. However, it is not effective in the treatment of sciatic neuropathic pain

Effects of silymarin on neuropathic pain and formalin- induced nociception in mice

Objective(s): Based on the previous reports, silymarin can suppress nitric oxide, prostaglandin E2 (PGE2), leukotrienes, cytokines production, and neutrophils infiltration. Regarding the fact that inflammation plays an important role in neuropathic and formalin-induced pain, it was assumed that silymarin could reduce pain. The present study investigates the analgesic effects of silymarin in chemical nociception and a model of neuropathic pain. Materials and Methods: Chemical nociception was produced by injection of 20 µl of formalin (0.5% formaldehyde in saline) into the plantar region of the right hind paw. A sciatic-nerve ligated mouse was applied as the model of neuropathic pain and the antinociceptive response of silymarin was examined 14 days after unilateral nerve-ligation using the hot plate test. Results: The intraperitoneal administration of silymarin (25, 50, and, 100 mg/kg) 2 hr prior to the intraplantar formalin injection suppressed the nociceptive response during the late phase of the formalin test significantly, but it was not in a dose-dependent manner. Different doses of silymarin 14 days after unilateral sciatic nerve ligation in hot plate test did not induce obvious antinociception. Conclusion: Results of the present study indicated that repeated administration of silymarin prevents the formalin-induced nociceptive behavior. However, it is not effective in the treatment of sciatic neuropathic pain

Auraptene consolidates memory, reverses scopolamine-disrupted memory in passive avoidance task, and ameliorates retention deficits in mice

Objective(s): Auraptene (7-geranyloxycoumarin) (AUR), from Citrus species has shown anti-inflammatory, neuroprotective, and acetylcholinesterase (AChE) and beta-secretase inhibitory effects. Scopolamine is a nonselective muscarinic receptor antagonist which causes short-term memory impairments and is used for inducing animal model of Alzheimer’s disease (AD). This research aimed to investigate the effect of AUR on scopolamine-induced avoidance memory retention deficits in step-through task in mice. Materials and Methods: The effect of four-day pre-training injections of AUR (50, 75, and 100 mg/kg, subcutaneous (SC)) and scopolamine (1 mg/kg, IP), and their co-administration on avoidance memory retention in step-through passive avoidance task, was investigated by measuring the latency to enter to the dark chamber. Results:Pre-training administration of AUR caused significant increase in step-through latency in comparison with control group, 48, 96, and 168 hr after training trial. The findings of this study showed that scopolamine (1 mg/kg, IP, for four consecutive days) impaired passive avoidance memory retention compared to saline-treated animals. Step-through passive avoidance task results showed that AUR markedly reversed scopolamine-induced avoidance memory retention impairments, 24 and 168 hr after training trial in step-through task. Conclusion: Results from co-administration of AUR and scopolamine showed that AUR reversed scopolamine-induced passive avoidance memory retention impairments

Bispecific monoclonal antibodies for targeted immunotherapy of solid tumors : Recent advances and clinical trials

Bispecific antibodie (BsAbs) combine two or more epitope-recognizing sequences into a single protein molecule. The first therapeutic applications of BsAbs were focused on cancer therapy. However, these antibodies have grown to cover a wider disease spectrum, including imaging, diagnosis, prophylaxis, and therapy of inflammatory and autoimmune diseases. BsAbs can be categorized into IgG-like formats and non-IgG-like formats. Different technologies have been used for the construction of BsAbs including "CrossMAb", "Quadroma", "knobs-into-holes" and molecular cloning. The mechanism of action for BsAbs includes the induction of CDC, ADCC, ADCP, apoptosis, and recruitment of cell surface receptors, as well as activation or inhibition of signaling pathways. The first clinical trials included mainly leukemia and lymphoma, but solid tumors are now being investigated. The BsAbs bind to a tumor-specific antigen using one epitope, while the second epitope binds to immune cell receptors such as CD3, CD16, CD64, and CD89, with the goal of stimulating the immune response against cancer cells. Currently, over 20 different commercial methods have been developed for the construction of BsAbs. Three BsAbs are currently clinically approved and marketed, and more than 85 clinical trials are in progress. In the present review, we discuss recent trends in the design, engineering, clinical applications, and clinical trials of BsAbs in solid tumors. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

Effect of gold nanoparticles on postoperative peritoneal adhesions in rats

Objective(s): Abdominal adhesions are one of the most important problems, occurring after intra-abdominal surgery in more than 90% of cases. This condition is the leading cause of bowel obstruction, infertility, and abdominal/pelvic pain. Gold nanoparticles (GNPs) have been shown to be non-toxic and exhibit anti-inflammatory, anti-angiogenic and antioxidant activities. The purpose of this study was to determine the effect of intraperitoneal lavage with GNP solutions on the development of postoperative peritoneal adhesion (PPA). Materials and Methods:In the current experimental study, thirty-five male Wistar rats were randomly assigned to seven groups of five rats. After a standardized peritoneal injury, GNP solutions in different concentrations (1, 2.5, 5, 10, 50 and 100 ng/ml) were locally administered through nebulization; normal saline (NS) was administered to the control group. Two weeks later, the rats were sacrificed and cecum and peritoneal samples were harvested for histopathological assessment. Blood samples were obtained to determine serum concentrations of inflammatory biomarkers including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and vascular endothelial growth factor (VEGF). Results: The rats treated with GNPs had significantly lower microscopic and macroscopic peritoneal adhesion scores, compared to the control group (