The alteration of chloride homeostasis/GABAergic signaling in brain disorders: Could oxidative stress play a role?

In neuronal precursors and immature neurons, the depolarizing (excitatory) effect of γ-Aminobutyric acid (GABA) signaling is associated with elevated [Cl−]i; as brain cells mature, a developmental switch occurs, leading to the decrease of [Cl−]i and to the hyperpolarizing (inhibi-tory) effect of GABAergic signaling. [Cl−]i is controlled by two chloride co-transporters: NKCC1, which causes Cl− to accumulate into the cells, and KCC2, which extrudes it. The ontogenetic up-regulation of the latter determines the above-outlined switch; however, many other factors contribute to the correct [Cl−]i in mature neurons. The dysregulation of chloride homeostasis is involved in seizure generation and has been associated with schizophrenia, Down’s Syndrome, Autism Spectrum Disorder, and other neurodevelopmental disorders. Recently, much effort has been put into developing new drugs intended to inhibit NKCC1 activity, while no attention has been paid to the origin of [Cl−]i dysregulation. Our study examines the pathophysiology of Cl− homeo-stasis and focuses on the impact of oxidative stress (OS) and inflammation on the activity of Cl− co-transporters, highlighting the relevance of OS in numerous brain abnormalities and diseases. This hypothesis supports the importance of primary prevention during pregnancy. It also inte-grates the therapeutic framework addressed to restore normal GABAergic signaling by counter-acting the alteration in chloride homeostasis in central nervous system (CNS) cells, aiming at lim-iting the use of drugs that potentially pose a health risk

Quantum repeaters and quantum key distribution: analysis of secret key rates

We analyze various prominent quantum repeater protocols in the context of long-distance quantum key distribution. These protocols are the original quantum repeater proposal by Briegel, D\"ur, Cirac and Zoller, the so-called hybrid quantum repeater using optical coherent states dispersively interacting with atomic spin qubits, and the Duan-Lukin-Cirac-Zoller-type repeater using atomic ensembles together with linear optics and, in its most recent extension, heralded qubit amplifiers. For our analysis, we investigate the most important experimental parameters of every repeater component and find their minimally required values for obtaining a nonzero secret key. Additionally, we examine in detail the impact of device imperfections on the final secret key rate and on the optimal number of rounds of distillation when the entangled states are purified right after their initial distribution.Comment: Published versio

Na+, K+-ATPase activity in children with autism spectrum disorder: Searching for the reason(s) of its decrease in blood cells

Na+, K+-ATPase (NKA) activity, which establishes the sodium and potassium gradient across the cell membrane and is instrumental in the propagation of the nerve impulses, is altered in a number of neurological and neuropsychiatric disorders, including autism spectrum disorders (ASD). In the present work, we examined a wide range of biochemical and cellular parameters in the attempt to understand the reason(s) for the severe decrease in NKA activity in erythrocytes of ASD children that we reported previously. NKA activity in leukocytes was found to be decreased independently from alteration in plasma membrane fluidity. The different subunits were evaluated for gene expression in leukocytes and for protein expression in erythrocytes: small differences in gene expression between ASD and typically developing children were not apparently paralleled by differences in protein expression. Moreover, no gross difference in erythrocyte plasma membrane oxidative modifications was detectable, although oxidative stress in blood samples from ASD children was confirmed by increased expression of NRF2 mRNA. Interestingly, gene expression of some NKA subunits correlated with clinical features. Excess inhibitory metals or ouabain-like activities, which might account for NKA activity decrease, were ruled out. Plasma membrane cholesterol, but not phosphatidylcholine and phosphatidlserine, was slighty decreased in erythrocytes from ASD children. Although no compelling results were obtained, our data suggest that alteration in the erytrocyte lipid moiety or subtle oxidative modifications in NKA structure are likely candidates for the observed decrease in NKA activity. These findings are discussed in the light of the relevance of NKA in ASD. Autism Research 2018. \ua9 2018 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay Summary: The activity of the cell membrane enzyme NKA, which is instrumental in the propagation of the nerve impulses, is severely decreased in erythrocytes from ASD children and in other brain disorders, yet no explanation has been provided for this observation. We strived to find a biological/biochemical cause of such alteration, but most queries went unsolved because of the complexity of NKA regulation. As NKA activity is altered in many brain disorders, we stress the relevance of studies aimed at understanding its regulation in ASD

A Multi-telescope Campaign on FRB 121102: Implications for the FRB Population

We present results of the coordinated observing campaign that made the first subarcsecond localization of a Fast Radio Burst, FRB 121102. During this campaign, we made the first simultaneous detection of an FRB burst by multiple telescopes: the VLA at 3 GHz and the Arecibo Observatory at 1.4 GHz. Of the nine bursts detected by the Very Large Array at 3 GHz, four had simultaneous observing coverage at other observatories. We use multi-observatory constraints and modeling of bursts seen only at 3 GHz to confirm earlier results showing that burst spectra are not well modeled by a power law. We find that burst spectra are characterized by a ~500 MHz envelope and apparent radio energy as high as $10^{40}$ erg. We measure significant changes in the apparent dispersion between bursts that can be attributed to frequency-dependent profiles or some other intrinsic burst structure that adds a systematic error to the estimate of DM by up to 1%. We use FRB 121102 as a prototype of the FRB class to estimate a volumetric birth rate of FRB sources $R_{FRB} \approx 5x10^{-5}/N_r$ Mpc$^{-3}$ yr$^{-1}$, where $N_r$ is the number of bursts per source over its lifetime. This rate is broadly consistent with models of FRBs from young pulsars or magnetars born in superluminous supernovae or long gamma-ray bursts, if the typical FRB repeats on the order of thousands of times during its lifetime.Comment: 17 pages, 7 figures. Submitted to AAS Journal

Design and Characterization of an Ethosomal Gel Encapsulating Rosehip Extract

: Rising environmental awareness drives green consumers to purchase sustainable cosmetics based on natural bioactive compounds. The aim of this study was to deliver Rosa canina L. extract as a botanical ingredient in an anti-aging gel using an eco-friendly approach. Rosehip extract was first characterized in terms of its antioxidant activity through a DPPH assay and ROS reduction test and then encapsulated in ethosomal vesicles with different percentages of ethanol. All formulations were characterized in terms of size, polydispersity, zeta potential, and entrapment efficiency. Release and skin penetration/permeation data were obtained through in vitro studies, and cell viability was assessed using an MTT assay on WS1 fibroblasts. Finally, ethosomes were incorporated in hyaluronic gels (1% or 2% w/v) to facilitate skin application, and rheological properties were studied. Rosehip extract (1 mg/mL) revealed a high antioxidant activity and was successfully encapsulated in ethosomes containing 30% ethanol, having small sizes (225.4 ± 7.0 nm), low polydispersity (0.26 ± 0.02), and good entrapment efficiency (93.41 ± 5.30%). This formulation incorporated in a hyaluronic gel 1% w/v showed an optimal pH for skin application (5.6 ± 0.2), good spreadability, and stability over 60 days at 4 °C. Considering sustainable ingredients and eco-friendly manufacturing technology, the ethosomal gel of rosehip extract could be an innovative and green anti-aging skincare product

Cytochalasin B Influences Cytoskeletal Organization and Osteogenic Potential of Human Wharton’s Jelly Mesenchymal Stem Cells

Among perinatal stem cells of the umbilical cord, human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) are of great interest for cell-based therapy approaches in regenerative medicine, showing some advantages over other MSCs. In fact, hWJ-MSCs, placed between embryonic and adult MSCs, are not tumorigenic and are harvested with few ethical concerns. Furthermore, these cells can be easily cultured in vitro, maintaining both stem properties and a high proliferative rate for several passages, as well as trilineage capacity of differentiation. Recently, it has been demonstrated that cytoskeletal organization influences stem cell biology. Among molecules able to modulate its dynamics, Cytochalasin B (CB), a cyto-permeable mycotoxin, influences actin microfilament polymerization, thus affecting several cell properties, such as the ability of MSCs to differentiate towards a specific commitment. Here, we investigated for the first time the effects of a 24 h-treatment with CB at different concentrations (0.1–3 μM) on hWJ-MSCs. CB influenced the cytoskeletal organization in a dose-dependent manner, inducing changes in cell number, proliferation, shape, and nanomechanical properties, thus promoting the osteogenic commitment of hWJ-MSCs, as confirmed by the expression analysis of osteogenic/autophagy markers

VALIDATION OF A MODIFIED MODEL OF TNBS-INDUCED COLITIS IN RATS. HOW TO INDUCE A CHEMICAL COLITIS IN RATS.

Background: there are no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic (TNBS) acid. Usually, the repeated administration of TNBS is preferred, because it will result in a local Th1 response that has the characteristics of Crohn's disease. material and Methods: A total of 30 rats were randomized into two groups, consisting of a saline control group of ten rats and a TNBS groups of 20 rats. After the animals were anesthesized, 0,5 ml of either 0,9 % saline 8controls) or TNBS 50 mg/Kg dissolved in 50% ethanol were instilled into the colon through a rubber catheter. The experiment was repeated weekly for four weeks, then, the rats were killed at day 40, and the distal colon removed. results: At day 40, the bowel wall basically normal in the control group. In the TNBS group, the bowel lumen became narrow with tickened wall, and the mucosal surface presented adherent membrane with brown black, linear ulcers, proliferous lymphocites tissue, inflammatory granulomas and submucosal neutrophil infiltration. The median score of the severity of the colonic damage was 0 in the control group, and 4,75 (range 4-5) in the TNBS group; the mean weight of the rats was 180+35 g in the TNBS group, while it was 215+25 in the control group. Conclusions: The presented experiment is a cost-effective and safe method to induce Crohn-like colonic damage using a lower dose of TNBS, thus avoiding the risk of a massive loss of rats. This model is rather suitable for the assessment of the effects of potential therapeutic agent

THE ROLE OF BUTYRIC ACID AS A OPROTECTIVE AGENT AGAINST INFLAMMATORY BOWEL DISEASE

Inflammatory Bowel disease (IBD), such as Crohn's disease and ulcerative colitis, are pathologies characterized by a chronic inflammation of the gastrointestinal tract. Their etiopathogenesis is not yet fully understood. Immune system and heat shock proteins (HSPs) dysfunctions are considered to be among the most likely causes of these diseases. Butyrate is a short-chain fatty acid produced by intestinal microflora. It has a trophic, benefical and protective role in the colonic mucosa, and it also induces changes in Hsp levels and localization. It may therefore be a valuable complementary therapeutic agent when used alongside trraditional drugs (mesalazine and corticosteroids) to treat the production of butyrate in the endoluminal environment may promote clinical remission in IBD patients. Due to these characteristics, there has been keen interest in the use of butyrate as a novel therapeutic supplement in the recent years. The current findings need to be validated through further clinical trials to better define the bbiomolecular dynamics of butyrate in the colonocytes of IBD patients

NUTRITION IN IBD PATIENT'S: WHAT ARE THE PROSPECTS?

Summary: Inflammatory Bowel Disease (IBD) is a chronic disorder characterized by a relapsing-remitting course, which alternates between active and quiescent states, ultimately impairing a patients quality of life. The two main types of IBD are Crohn's disease (CD) and Ulcerative Colitis (UC). In physiological conditions the gut is costantly exposed to various antigens, commensal microflora and pathogens and the inflammatory response is finely balanced. It is thought that a vast number of environmental risk factors may be implicated in the development of IBD, including smoking factors, dietary factors, psycological stress, use of non-steroidal anti-inflammatory drugs and oral contraceptives, appendicectomy, breastfeeding, as well as infections. Nutritional support, as a primary therapy, has a crucial role in the management of patients with IBD. The gut microbiota is clearly manipulated by dietary components such as n-3 polyunsatured fatty acids (n-3 PUFA) and coniugated linoleic acid (CLA) which favorably reduce endotoxin load via shifts in the composition and metabolic activity of the microbial community. in particular, the beneficial effect of n-3 PUFAs and fermentable fiber, during the remission/quiescent phase of both CD and UC is Highlighted. In fact, PUFAs are associated with a less grade of inflammation since they are metabolized to 3-series prostagliandins and thromboxanes and 5-series leukotrienes and, in addition, exert antiinflammatory effects when compared with their n-6 PUFA counterparts. In similar action to dietary n-3 PUFA, coniugated linoleic acid (CLA) have been reported to ameliorate intestinal inflammation in animal models of IBD. Currently, is still unclear the role of the fibers in helping the remission of the disease. Data about the consumption of fiber are controversial. On one hand, dietary fibers can act as effective prebiotics by altering the intestinal microbial composition and promoting the growth of beneficial bacterial communities within the large intestine. On the other hand, fibers can promote diarrhea, pain and gas aggravating the clinical sate. Cocnclusion: We suggest that the consumption of fermentable fibers may have a good impact on patient's health