The role of nanotechnology in current COVID-19 outbreak.

COVID-19 has recently become one of the most challenging pandemics of the last century with deadly outcomes and a high rate of reproduction number. It emphasizes the critical need for the designing of efficient vaccines to prevent virus infection, early and fast diagnosis by the high sensitivity and selectivity diagnostic kits, and effective antiviral and protective therapeutics to decline and eliminate the viral load and side effects derived from tissue damages. Therefore, non-toxic antiviral nanoparticles (NPs) have been under development for clinical application to prevent and treat COVID-19. NPs showed great promise to provide nano vaccines against viral infections. Here, we discuss the potentials of NPs that may be applied as a drug itself or as a platform for the aim of drug and vaccine repurposing and development. Meanwhile, the advanced strategies based on NPs to detect viruses will be described with the goal of encouraging scientists to design effective and cost-benefit nanoplatforms for prevention, diagnosis, and treatment.

Acidic pH derived from cancer cells as a double-edged knife modulates wound healing through DNA repair genes and autophagy.

Wound healing is a sequester program that involves diverse cell signalling cascades. Notwithstanding, complete signal transduction pathways underpinning acidic milieu derived from cancer cells is not clear, yet. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, fluorescein diacetate/propidium iodide staining, and cell cycle flow cytometry revealed that acidic media decreased cell viability and cell number along with enhanced dead cells and S-phase arrest in normal fibroblasts. Notably, the trends of intracellular reactive oxygen species production and lactate dehydrogenase release significantly increased with time. It seems the downregulation of Klf4 is in part due to acidosis-induced DNA damage. It promoted cells towards S-phase arrest and diminished cell proliferation. Klf4 downregulation had a direct correlation with the P53 level while acidic microenvironment promotes cells towards cell death mechanisms including apoptosis and autophagy. Noteworthily, the unchanged levels of Rb and Mlh1 indicated in those genes had no dominant role in the repairing of DNA damage in fibroblasts treated with the acidic microenvironment. Therefore, cells owing to not entering to mitosis and accumulation of DNA damage were undergone cell death to preserve cell homeostasis. Since acidic media decreased the level of tumour suppressor and DNA repair genes and altered the normal survival pathways in fibroblasts, caution should be exercised to not lead to cancer rather than wound healing.

Hybrid and Composite Scaffolds Based on Extracellular Matrices for Cartilage Tissue Engineering.

IMPACT STATEMENT: Scaffolds fabricated from extracellular matrix (ECM) derivatives are composed of conducive structures for cell attachment, proliferation, and differentiation, but generally do not have proper mechanical properties and load-bearing capacity. In contrast, scaffolds based on synthetic biomaterials demonstrate appropriate mechanical strength, but the absence of desirable biological properties is one of their main disadvantages. To integrate mechanical strength and biological cues, these ECM derivatives can be conjugated with synthetic biomaterials. Hence, hybrid scaffolds comprising both advantages of synthetic polymers and ECM derivatives can be considered a robust vehicle for tissue engineering applications.

Transplantation of Adipose Tissue-Derived Stem Cells into Brain Through Cerebrospinal Fluid in Rat Models: Protocol Development and Initial Outcome Data.

BACKGROUND: Cell therapy is an important strategy for the treatment of incurable diseases including those that occur in the Central Nervous System (CNS). Among different strategies, the method of delivering or transplantation of cells into the brain has shown significant effects on regeneration. In this study, a new protocol has been developed for the transplantation of adipose tissuederived stem cells into the brain through Cerebrospinal Fluid (CSF) in rat models. METHODS: For this purpose, a wide range of ages (7-30 days old) of male neonates of Wistar rats was used. Moreover, human adipose tissue was obtained from a superficial layer of abdomen through liposuction surgery. The size of the inserted part of needle to access middle cranial fossa and subarachnoid space in animals with an average weight of 10-80 g was determined. In addition, to confirm the entrance of needle into the subarachnoid space, CSF was aspirated slowly and then injection was done within two minutes. RESULTS: The findings showed the presence of transplanted human Adipose-Derived Stem Cells (hADSC) in the cerebellum and basal ganglia following three days and also after two months that confirmed the entrance of transplanted cells into the cerebrospinal fluid and migration of them into the brain tissue. All the animals survived after the transplantation process, with the lowest side effects compared to the available conventional methods. CONCLUSION: It can be concluded that the cells could be efficiently transplanted into CSF through subarachnoid space by injection via superior orbital fissure with a minimally invasive technique.

Targeting axonal degeneration and demyelination using combination administration of 17ß-estradiol and Schwann cells in the rat model of spinal cord injury.

Schwann cells (SCs) are known to be responsible for axonal ensheathing and myelination, and their transplantation is used commonly for treatment of spinal cord injury (SCI). 17ß-estradiol (E2) has also reported for its protective roles in neurons in the transplanted SCs to the SCI model. In the current study, we evaluated the roles of E2 administration before SCs transplantation in targeting SCI-induced axonal degeneration and demyelination. E2 (25 µg/kg, IP) was administered to the male Wistar rats underwent contusive SCI at T10 segment. At 7 days after injury, 1 × 106 SCs were transplanted to the injury epicenter of the spinal cord. The groups were laminectomy, SCI, SCI+E2, and SCI+E2+SCs. Functional recovery was evaluated using the Basso-Bresnahan-Beattie locomotor test. Sections from spinal cord were also assessed for histoloical staining, including Luxol fast blue, Bielschowsky's silver and immunofluorescence evaluation of myelin basic protein (MBP). The SCI group showed impaired locomotion in the hind limb, increased number of cavities within spinal cord, low observable numbers of regenerating fibers, and a significant decrease in the rate of expression for MBP. These changes were counteracted in the treatment groups ( P < 0.05 vs SCI) with no significant changes among them. From the results, it may be concluded that application of E2 and SCs could be effective when axons undergo demyelination and degenerative processes, and their combination could partly provide cumulative outcomes.

Protocol for Three-dimensional Confocal Morphometric Analysis of Astrocytes.

As glial cells in the brain, astrocytes have diverse functional roles in the central nervous system. In the presence of harmful stimuli, astrocytes modify their functional and structural properties, a condition called reactive astrogliosis. Here, a protocol for assessment of the morphological properties of astrocytes is presented. This protocol includes quantification of 12 different parameters i.e. the surface area and volume of the tissue covered by an astrocyte (astrocyte territory), the entire astrocyte including branches, cell body, and nucleus, as well as total length and number of branches, the intensity of fluorescence immunoreactivity of antibodies used for astrocyte detection, and astrocyte density (number/1,000 µm(2)). For this purpose three-dimensional (3D) confocal microscopic images were created, and 3D image analysis software such as Volocity 6.3 was used for measurements. Rat brain tissue exposed to amyloid beta1-40 (Aß1-40) with or without a therapeutic intervention was used to present the method. This protocol can also be used for 3D morphometric analysis of other cells from either in vivo or in vitro conditions.

Slow oscillating transcranial direct current stimulation during sleep has a sleep-stabilizing effect in chronic insomnia: a pilot study.

Recent evidence suggests that lack of slow-wave activity may play a fundamental role in the pathogenesis of insomnia. Pharmacological approaches and brain stimulation techniques have recently offered solutions for increasing slow-wave activity during sleep. We used slow (0.75 Hz) oscillatory transcranial direct current stimulation during stage 2 of non-rapid eye movement sleeping insomnia patients for resonating their brain waves to the frequency of sleep slow-wave. Six patients diagnosed with either sleep maintenance or non-restorative sleep insomnia entered the study. After 1 night of adaptation and 1 night of baseline polysomnography, patients randomly received sham or real stimulation on the third and fourth night of the experiment. Our preliminary results show that after termination of stimulations (sham or real), slow oscillatory transcranial direct current stimulation increased the duration of stage 3 of non-rapid eye movement sleep by 33 ± 26 min (P = 0.026), and decreased stage 1 of non-rapid eye movement sleep duration by 22 ± 17.7 min (P = 0.028), compared with sham. Slow oscillatory transcranial direct current stimulation decreased stage 1 of non-rapid eye movement sleep and wake time after sleep-onset durations, together, by 55.4 ± 51 min (P = 0.045). Slow oscillatory transcranial direct current stimulation also increased sleep efficiency by 9 ± 7% (P = 0.026), and probability of transition from stage 2 to stage 3 of non-rapid eye movement sleep by 20 ± 17.8% (P = 0.04). Meanwhile, slow oscillatory transcranial direct current stimulation decreased transitions from stage 2 of non-rapid eye movement sleep to wake by 12 ± 6.7% (P = 0.007). Our preliminary results suggest a sleep-stabilizing role for the intervention, which may mimic the effect of sleep slow-wave-enhancing drugs.

The effect of tiagabine on physical development and neurological reflexes and their relationship with the γ-aminobutyric acid switch in the rat cerebral cortex during developmental stages.

In the present study, we focused on γ-aminobutyric acid (GABA) signaling through the γ-aminobutyric acid transporter (GAT) in the developing rat cerebral cortex. Tiagabine was used as a GAT inhibitor. The offspring received injections from birth until postnatal day 21 intraperitoneally. Physical development and neurological reflexes were assessed daily. Tiagabine did not influence body weight, the onset and completion of incisor eruption, or the time to appearance of cliff avoidance. However, the onset and completion of eye opening, ear unfolding, and fur growth occurred earlier in treated pups. Further, the slanted board test and righting reflex showed accelerated development (i.e. decreased time to criterion) when compared with the control group. To determine whether the obtained effects are related to the GABA switch, we examined the protein and mRNA expression of the K(+)-Cl(-) cotransporter KCC2 using western blotting and RT-PCR, respectively. Downregulation of KCC2 mRNA and protein levels was observed when GAT was inhibited. The results may indicate a role of GAT in the neurobehavioral changes that accompany the developmental switch in GABA function.

High complement factor I activity in the plasma of children with autism spectrum disorders.

Autism spectrum disorders (ASDs) are neurodevelopmental and behavioural syndromes affecting social orientation, behaviour, and communication that can be classified as developmental disorders. ASD is also associated with immune system abnormality. Immune system abnormalities may be caused partly by complement system factor I deficiency. Complement factor I is a serine protease present in human plasma that is involved in the degradation of complement protein C3b, which is a major opsonin of the complement system. Deficiency in factor I activity is associated with an increased incidence of infections in humans. In this paper, we show that the mean level of factor I activity in the ASD group is significantly higher than in the control group of typically developed and healthy children, suggesting that high activity of complement factor I might have an impact on the development of ASD.