Use of Mometasone furoate in prolonged treatment of experimental spinal cord injury in mice: A comparative study of three different glucocorticoids

Traumatic spinal cord injury (SCI) represents one of the most disabling injuries of the human body causing temporary or permanent sensory and/or motor system deficit, particularly hind limb locomotor function impairment. At present, steroidal inflammatory drugs, in particular methylprednisolone sodium succinate (MPSS) are the first line choice treatment of acute SCI. Despite progress in pharmacological, surgical and rehabilitative treatment approaches, SCI still remains a very complex medical and psychological challenge, with no curative therapy available. The aim of the present study was to compare the efficacy of MPSS in respect to other GCs such as dexamethasone (Dex) and mometasone furoate (MF) in an in vitro suitable model of LPS-induced inflammation in J774 cells as well as in an in vivo experimental mouse SCI (compression model). In both the in vitro and in vivo experiments, MF resulted surprisingly more potent than Dex and MPSS. In detail, mice sacrificed seven days after induction of SCI trauma resulted not only in tissue damage, cellular infiltration, fibrosis, astrocyte activation, iNOS expression, extracellular signal regulated kinase 1/2 phosphorylation in injured tissue, poly (ADP-ribose) polymerase 1 (PARP-1) activation but also apoptosis (Bax and Bcl-2 expression). All three GCs demonstrated the ability to modulate inflammatory, oxidative as well as apoptotic pathways, but MF demonstrated the best efficacy, while Dex and MPSS showed alternative potency with a different degree of protection. Therefore, we can conclude that MF is the best candidate for post-traumatic chronic treatment, since it ameliorates different molecular pathways involved in the damage's propagation to the surrounding areas of the injured spinal cord

Alternative source of stem cells derived from human periodontal ligament: a new treatment for experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is categorized as an autoimmune disease and is potentially one of the most common causes of neurological disability in young adults. Formation of the sclerotic plaques of which the disease gets its name represents the end stage of a process involving inflammation, demyelination and remyelination, oligodendrocytes depletion, and astrogliosis as well as neuronal and axonal degeneration (1). MS damages the central nervous system and leads to a disabling condition. Recently, the potential role of mesenchymal stem cells (MSCs), derived in promoting tissue repair and disease control has been investigated by using an experimental autoimmune encephalomyelitis (EAE) model (2). The objective of the research was to investigate the product effects by mesenchymal stem cells derived from human periodontal ligament (hPDLSCs) when administered in an experimental model of autoimmune encephalomyelitis (EAE). EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG)35-55 in C57BL/6 mice. Then, mice were observed every 48 hours for signs of EAE and weight loss. At the onset of disease, approximately 14 days after immunization, EAE mice were subjected to a single intravenous injection of hPDLSCs (10(6) cells/150 μl) into the tail vein. At the point of animal sacrifice on day 56 after EAE induction, spinal cord and brain tissues were collected in order to perform histological evaluation, immunohistochemistry and western blotting analysis. Obtained results reveal that treatment with hPDLSCs may produce neuroprotective effects against EAE, diminishing both clinical signs and histological score typical of the disease (lymphocytic infiltration and demyelination) probably through the production of neurotrophic factors (results focused on brain-derived neurotrophic factor and nerve growth factor expression). Furthermore, administration of hPDLSCs modulates expression of inflammatory key markers (tumor necrosis factor-α, interleukin (IL)-1β, IL-10, glial fibrillary acidic protein, Nrf2 and Foxp3), the release of CD4 and CD8α T cells, and the triggering of apoptotic death pathway (data shown for cleaved caspase 3, p53 and p21). In light of the achieved results, transplantation of hPDLSCs may represent a putative novel and helpful tool for multiple sclerosis treatment. These cells could have considerable implication for future therapies for multiple sclerosis and this study may represent the starting point for further investigations

Engineered vesiscles from gingival stem cells: a new approach in 3D printed bone tissue regeneration

In the bone regeneration field, properties of 3D scaffold could be improved using cellular and their released products. Even if previously documented, poly-(lactide) (PLA) scaffolds were not thoroughly evaluated for their design-related characteristics. The aim of the study was to investigate the properties of 3D printed PLA scaffolds for bone regeneration obtained through 3D printing, evaluating the differences in terms of structural properties, in vitro and in vivo cellular responses induced by different scaffold structures. Biofabrication is to generate a construct with biological function. In particular in our reserach we describe the fully process, including printing scaffold step, in vitro culture phase and subsequently in vivo transplantation. Five porous scaffold designs (A-B-C-D-E) were fabricated from a poly-(lactide) (PLA) filament. Scaffold structural parameters, such as porosity and pore size, were measured using scanning electron microscopy, and micro-computed tomography. Nano-topographic surface features were investigated by means of atomic force microscopy. Over a 112-day period, scaffolds were hydrolytically degraded and changes in weight, pH and mechanical properties were measured during degradation. Osteogenic differentiation of hPDLSCs on different scaffold designs after 21 days of culture was measured by means of RT-PCR and Western Blot. In vivo study was performed using C57BL/6 mice and was designed in 5 different groups: - Group1: Scaffold loaded with hPDLSCs - Group2: Scaffold loaded with conditioned medium (CM) derived from hPDLSCs - Group3: Scaffold loaded with exosomes (Exo) purified from CM - Group 4: Scaffold loaded with engineered exosomes (e-Exo), exosome treated with PEI (poly ether imide) - Group5: Scaffold, used as control. Histological analysis were performed after 60 days of in vivo transplantation and morphological evaluations revealed a high bone tissue formation and osteogenic cells commitment in group 3 and 4 when compared to other groups. From these results, the cell-laden PCAMSC scaffold offers a significant advantage in the TM regeneration in a rat subacute TM perforation model. It may offer attractive opportunities in the conservative clinical treatment. This study demonstrated that scaffold of group 3 and 4 significantly improved bone tissue regeneration in animal model and successfully showed new bone deposition in situ compared to the control scaffold (group 5) and group 1 and 2. Based on the results, we believe that the bioprinted scaffold may become a novel treatment for tissue regeneration approach therapy

Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases

Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated

Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic ap-proaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids

Moringa isothiocyanate complexed with α-cyclodextrin: a new perspective in neuroblastoma treatment

Abstract Background Several lines of evidence suggest the consume of natural products for cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting anti-cancer properties, have received great interest as potential chemotherapeutic agents. This study was designed to assess the anti-proliferative activities of a new preparation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl ITC (moringin) complexed with alpha-cyclodextrin (moringin + α-CD; MAC) on SH-SY5Y human neuroblastoma cells. This new formulation arises in the attempt to overcome the poor solubility and stability of moringin alone in aqueous media. Methods SH-SY5Y cells were cultured and exposed to increasing concentrations of MAC (1.0, 2.5 and 5.0 μg). Cell proliferation was examined by MTT and cell count assays. The cytotoxic activity of the MAC complex was assessed by lactate dehydrogenase (LDH) assay and trypan blue exclusion test. In addition, western blotting analyses for the main apoptosis-related proteins were performed. Results Treatment of SH-SY5Y cells with the MAC complex reduced cell growth in concentration dependent manner. Specifically, MAC exhibited a potent action in inhibiting the PI3K/Akt/mTOR pathway, whose aberrant activation was found in many types of cancer. MAC was also found to induce the nuclear factor-κB (NF-κB) p65 activation by phosphorylation and its translocation into the nucleus. Moreover, treatment with MAC was able to down-regulate MAPK pathway (results focused on JNK and p38 expression). Finally, MAC was found to trigger apoptotic death pathway (based on expression levels of cleaved-caspase 3, Bax/Bcl-2 balance, p53 and p21). Conclusion These findings suggest that use of MAC complex may open novel perspectives to improve the poor prognosis of patients with neuroblastoma

Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview

The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common. Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required. In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia. In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia. We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia

A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis

BACKGROUND: The present study was designed to investigate the efficacy of a new formulation of alone, purified cannabidiol (CBD) (>98 %), the main non-psychotropic cannabinoid of Cannabis sativa, as a topical treatment in an experimental model of autoimmune encephalomyelitis (EAE), the most commonly used model for multiple sclerosis (MS). Particularly, we evaluated whether administration of a topical 1 % CBD-cream, given at the time of symptomatic disease onset, could affect the EAE progression and if this treatment could also recover paralysis of hind limbs, qualifying topical-CBD for the symptomatic treatment of MS. METHODS: In order to have a preparation of 1 % of CBD-cream, pure CBD have been solubilized in propylene glycoland basic dense cream O/A. EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG35–55) in C57BL/6 mice. After EAE onset, mice were allocated into several experimental groups (Naïve, EAE, EAE-1 % CBD-cream, EAE-vehicle cream, CTRL-1 % CBD-cream, CTRL-vehicle cream). Mice were observed daily for signs of EAE and weight loss. At the sacrifice of the animals, which occurred at the 28(th) day from EAE-induction, spinal cord and spleen tissues were collected in order to perform histological evaluation, immunohistochemistry and western blotting analysis. RESULTS: Achieved results surprisingly show that daily treatment with topical 1 % CBD-cream may exert neuroprotective effects against EAE, diminishing clinical disease score (mean of 5.0 in EAE mice vs 1.5 in EAE + CBD-cream), by recovering of paralysis of hind limbs and by ameliorating histological score typical of disease (lymphocytic infiltration and demyelination) in spinal cord tissues. Also, 1 % CBD-cream is able to counteract the EAE-induced damage reducing release of CD4 and CD8α T cells (spleen tissue localization was quantified about 10,69 % and 35,96 % of positive staining respectively in EAE mice) and expression of the main pro-inflammatory cytokines as well as several other direct or indirect markers of inflammation (p-selectin, IL-10, GFAP, Foxp3, TGF-β, IFN-γ), oxidative injury (Nitrotyrosine, iNOS, PARP) and apoptosis (Cleaved caspase 3). CONCLUSION: All these data suggest an interesting new profile of CBD that could lead to its introduction in the clinical management of MS and its associated symptoms at least in association with current conventional therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40199-015-0131-8) contains supplementary material, which is available to authorized users