Robbinsthorhauge8996
The survey covered what pathways were affected, how the immune responses were presented, how the company and health authorities interpreted the data and whether the immune responses were observed in the clinic. Additionally, the survey gathered information on association of these findings with anti-drug antibodies as well as sponsor's use of immunogenicity predictive tools. The data suggests that the ability of a biotherapeutic to activate the immune system, intended or not, plays a significant role on characteristics of the response and whether theys are translatable.Cannabinoids have been shown to protect the retina from ischemic/excitotoxic insults. Brequinar The aim of the present study was to investigate the neuroprotective and anti-inflammatory properties of the synthetic cannabinoid (R)-WIN55,212-2 (CB1/CB2 receptor agonist) when administered acutely or subchronically in control and AMPA treated retinas. Sprague-Dawley rats were intravitreally administered (acutely) with vehicle or AMPA, in the absence or presence of (R)-WIN55,212-2 (10-7-10-4M) alone or in combination with AM251 [CB1 receptor antagonist/inverse agonist,10-4M] and AM630 (CB2 receptor antagonist,10-4M). In addition, AMPA was co-administered with the racemic (R,S)-WIN55,212 (10-4Μ). (R)-WIN55,212-2 was also administered subchronically (25,100 μg/kg,i.p.,4d) in control and AMPA treated rats. Immunohistochemical studies were performed using antibodies against the CB1R, and retinal markers for retinal neurons (brain nitric oxide synthetase, bNOS) and microglia (ionized calcium binding adaptor molecule 1, Iba1). ELsub-chronically, on neuron viability and microglia activation in healthy and diseased retina.Pomegranate (Punica granatum) fruit is of particular interest because of its high nutritional value and therapeutic actions. Recently, we showed that an aqueous extract of pomegranate (AE-PG) given by oral route induced antidepressant-like actions mediated by estrogen receptors (ERs) suggesting its potential to function as an alternative to estrogen therapy replacement in menopause-related depression treatment. Orally administered AE-PG allows the biotransformation of ellagitannins into active estrogenic compounds through the intestinal microbiota. However, it is necessary to know if compounds that do not need to be biotransformed by the intestinal microbiota are involved in the antidepressant-like effects. Therefore, the first aim of this study was to determine if AE-PG produces an antidepressant-like effect when administered intraperitoneally. Also, to determine the participation of specific ER-subtypes (α or β) and to analyze the role of the serotonergic system. Young female Wistar rats were ovariectomized as a surgical model of menopause. The intraperitoneal administration of AE-PG (1 mg/kg; i. p.) was evaluated in the forced swimming test and open field tests. Also, the ERα antagonist (TPBM; 50 μg/rat; s. c.) or the ERβ antagonist (PHTPP; 25 μg/rat; s. c.) were administered with AE-PG to analyze the participation of the specific ERs. Finally, the effect of the serotonin neurotoxin 5,7-DHT (200 μg/rat; i. c.v.) on the antidepressant-like effect of the AE-PG was studied in independent experimental groups. RESULTS showed that AE-PG administered by intraperitoneal route induced antidepressant-like effects. This result suggests that gut microbiota biotransformation is not necessary to exert its actions. The mechanism of action involves the activation of the ERβ and the serotonergic system. Altogether, this information contributes to the elucidation of the antidepressant action of the pomegranate fruit, which could be further considered as an alternative treatment for depression during menopause.Stroke leads to significant neuronal death and long-term neurological disability due to synergistic pathogenic mechanisms. Stroke induces a change in eating habits and in many cases, leads to undernutrition that aggravates the post-stroke pathology. Proper nutritional regimen remains a major strategy to control the modifiable risk factors for cardiovascular and cerebrovascular diseases including stroke. Studies indicate that nutraceuticals (isolated and concentrated form of high-potency natural bioactive substances present in dietary nutritional components) can act as prophylactic as well as adjuvant therapeutic agents to prevent stroke risk, to promote ischemic tolerance and to reduce post-stroke consequences. Nutraceuticals are also thought to regulate blood pressure, delay neurodegeneration and improve overall vascular health. Nutraceuticals potentially mediate these effects by their powerful antioxidant and anti-inflammatory properties. This review discusses the studies that have highlighted the translational potential of nutraceuticals as stroke therapies.Autism spectrum disorder (ASD) is characterized by the expression of restricted repetitive behaviors (RRBs) and impairments in social recognition and communication. Previous studies have found that specific serotonin (5-HT) receptor modulation can attenuate repetitive behaviors expressed in specific mouse strains. The present study examined how 5-HT6 receptor blockade impacts the expression of repetitive behaviors in two different mouse strains that demonstrate elevated restricted, repetitive behavior and impairments in social behavior. BTBR T+ Itpr3tf /J (BTBR), C58/J (C58) and control C57BL/6J strains were behaviorally tested after acute treatment with the 5-HT6 receptor antagonist BGC 20-761 (BGC) or vehicle. BTBR mice express high levels of self-grooming behavior while C58 mice display high rates of repetitive jumping behavior. Similarly, the effect of 5-HT6 receptor blockade was also tested on social approach behaviors in both strains. BGC significantly reduced repetitive grooming in both female and malecific to the types of repetitive behaviors expressed.Graft-versus-host disease (GVHD) is a frequent complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The application of mesenchymal stromal cells (MSCs) to treat GVHD patients refractory to initial steroid treatment has led to impressive results. In this study, we explored the potential of human umbilical mesenchymal stem cells (HUMSCs) transfected with the IFN-γ gene of human (h)/mice (m) (HUMSCs + Ad-h/mIFN-γ) carried by a recombinant adenoviral vector in the prevention and treatment of GVHD. We demonstrated that HUMSCs + Ad-h/mIFN-γ efficiently suppressed T lymphocyte proliferation and activation, induced G1 cell cycle arrest and apoptosis in vitro. To assess the in vivo efficacy of HUMSCs + Ad-h/mIFN-γ, Balb/c mice were induced to develop GVHD symptoms by tail vein injection of C57BL/6 splenocytes after irradiation. Weight, hair, survival, hemogram, and chimera condition of GVHD model mice were monitored before and after treatment, respectively. The results showed that HUMSCs + Ad-h/mIFN-γ reduced GVHD's incidence and severity on the model mice and provided a significant survival benefit.