High accuracy of a blood ctDNA-based multimodal test to detect colorectal cancer.

Background: Detection of circulating tumor DNA (ctDNA) is a minimally invasive and convenient blood-based screening strategy that may increase effectiveness of colorectal cancer (CRC) screening.

Patients And Methods: A novel multimodal ctDNA-based blood assay that integrates genomics, epigenomics and fragmentomics, as well as proteomics in a refined version, was tested in blood samples from two cohorts: (i) consecutive fecal immunochemical test (FIT)-positive individuals from the CRC Barcelona stool-based screening program; (ii) patients diagnosed with CRC. Primary endpoint was the performance of the test to detect CRC at different tumor-node-metastasis (TNM) stages.

Development of Peptide-Based PDZ Domain Inhibitors.

Over the past decades, peptide-based drugs have gained increasing interest in a wide range of treatment applications, primarily because of high potency and selectivity, as well as good efficacy, tolerability, and safety often achieved with peptides. Attempts to target postsynaptic density protein of 95 (PSD-95) PSD-95/Discs large/Zonula occludens-1 (PDZ) domains, which mediate the formation of a ternary complex with the N-methyl-D-aspartate (NMDA) receptor and neuronal nitric oxide synthase (nNOS) responsible for excitotoxicity in ischemic stroke, by high-affinity small molecules have failed in the past. In this chapter, we focus on the discovery of peptide-based drugs targeting PSD-95, using AVLX-144 as an example, from the synthesis, over binding assays to its target, to further in vitro experiments based on the development of AVLX-144, a potential stroke treatment, which is planned to enter clinical trials in 2020.

A quasi-monoenergetic short time duration compact proton source for probing high energy density states of matter.

We report on the development of a highly directional, narrow energy band, short time duration proton beam operating at high repetition rate. The protons are generated with an ultrashort-pulse laser interacting with a solid target and converted to a pencil-like narrow-band beam using a compact magnet-based energy selector. We experimentally demonstrate the production of a proton beam with an energy of 500 keV and energy spread well below 10[Formula: see text], and a pulse duration of 260 ps.

Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from Neisseria meningitidis serogroup B.

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N.

Detection of oocyst-associated toxoplasmosis in swine from southern Chile.

Pork has been traditionally considered an important source of human Toxoplasma gondii infection. Pigs, as other meat-producing animals, can become infected by the ingestion of oocysts that are shed in the environment by infected cats or by the consumption of cysts present in tissues of infected mammals, commonly small rodents. The objective of this study was to investigate the level of T.

Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations.

Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens.

The golden era of vaccine adjuvants.

A 5-day workshop on adjuvant for vaccines was held in Trinidad, Cuba, on the 16-21 May 2010. Organized by the Latin American Association for Immunology and the Cuban Society for Immunology, the workshop attracted more than 60 scientists from different parts of the world. The meeting summarizes current knowledge regarding vaccine adjuvants, including delivery systems and parasitic vaccines.

AFCo1 as nasal adjuvant of capsular polysaccharide from Neisseria meningitidis serogroup C induces systemic and mucosal immune responses.

Increasing emphasis is being placed on the mucosal administration of vaccines in order to stimulate mucosal as well as systemic responses. Findings from our group suggest that proteoliposome-derived cochleate (AFCo1) acts as a potent mucosal adjuvant. As an alternative to chemical conjugation, the current study aimed to determine the benefit of using AFCo1 to improve the mucosal and systemic immune responses to capsular polysaccharide of Neisseria meningitidis serogroup C (PsC), a model of a thymus-independent (TI) antigen.

Mucosal and systemic immune responses of mice to tetanus toxoid coadministered nasally with AFCo1.

Mucosal immune responses are an early and important line of defense against pathogens. The current understanding of the mucosal immune system allows us to consider the use of nasal immunization for induction of antigen-specific immune responses at the mucosal surface and the systemic compartment. Mucosal adjuvants are key for developing novel mucosal vaccines and represent 1 approach to improving mucosal and systemic immunity.

Effects of resveratrol on expression of vascular endothelial growth factor in human gingival fibroblasts stimulated by periodontal pathogens.

Objective: To investigate the effects of resveratrol, a naturally occurring polyphenol, on the expression of vascular endothelial growth factor (VEGF) in human gingival fibroblast culture in response to vesicles and outer membrane proteins from periodontopathic bacteria.

Material And Methods: Human gingival fibroblasts were stimulated with vesicles and outer membrane proteins from Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. In human gingival fibroblast cultures treated with or without resveratrol, VEGF production was evaluated by means of enzyme-linked immunosorbent assay and VEGF mRNA expression by means of reverse transcription polymerase chain reaction analysis.

Effects of psychological stress and fluoxetine on development of oral candidiasis in rats.

Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans. Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed experiments to evaluate the effects of fluoxetine on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor.

Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses.

Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen.

Effects of amphetamine and cocaine on the development of acute experimental allergic encephalomyelitis in Lewis rats.

The present experiment deals with the effects of amphetamine and cocaine on the development and course of experimental allergic encephalomyelitis (EAE) induced in Lewis rats. Rats were immunized at the age of eight weeks with purified myelin basic protein isolated from guinea pig brain in complete Freund's adjuvant. Drug administration and recording of EAE clinical signs was performed daily since day 1 post-immunization (PI).

New vaccines require potent adjuvants like AFPL1 and AFCo1.

Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative-Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen-associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non-related antigens.

Adjuvant properties of lipopolysaccharide from Neisseria meningitidis serogroup B detoxified and conjugated with tetanus toxoid.

We evaluated the adjuvant properties and toxicity of purified Neisseria meningitidis serogroup B lipopolysaccharide (LPS) conjugated with tetanus toxoid (TT) using a new method of conjugation to obtain amine groups in the polysaccharide structure. The endotoxic activity of treated LPS was reduced 2400 times as determined by Limulus amoebocyte assay and no mortality was observed in Balb/c mice inoculated with detoxified LPS versus 100% mortality in native LPS inoculated mice. The conjugated LPS-TT elicited in mice higher anti-TT IgG2a and IgG1 than unconjugated TT.

Effects of fluoxetine on cellular immune response in stressed mice.

We studied the effects of fluoxetine, a non-tricyclic antidepressant drug that selectively inhibits re-uptake of serotonin by presinaptic neurons in the brain, on cellular immune responses in mice exposed to a chronic auditory stressor. The natural killer (NK) cell activity was reduced after 4, 8, 12, 16 and 20 days of stress exposure with a partial recovery on days 16 and 20. Daily treatment with fluoxetine partially reversed these adverse effects of stress in a dose-dependent manner.

Effects of nefazodone on the development of experimentally induced tumors in stressed rodents.

Rationale: Anxiety and depression are commonly encountered in patients with cancer and constitute risk and prognostic factors for the disease. Although previous findings do not support an overall association between the use of antidepressants and higher prevalence of cancer, results for serotonin uptake inhibitors are not entirely reassuring.

Objectives: We evaluated the effects of nefazodone, a serotonin and norepinephrine (NE) reuptake inhibitor and 5-HT(2A) receptor antagonist antidepressant, on the appearance of breast cancer induced by mammary tumor virus (MTV) in mice, and on the development of lung metastases in rats injected intravenously with Walker 256 (W-256) carcinosarcoma cells.

Serotonin upregulates the activity of phagocytosis through 5-HT1A receptors.

1 In this study, we investigated whether serotonin could regulate the in vitro activity of phagocytosis through 5-hydroxytryptamine or serotonin (5-HT(1A)) receptors. 2 Mouse peritoneal macrophages were cultured with serotonin and the activity of phagocytosis was assessed by the uptake of zymosan and latex particles added to the culture media. Specific binding of [(3)H]8-OH-DPAT and immunohistochemistry using an affinity-purified anti-5-HT(1A)-receptor antibody were assayed in the macrophages.

Administration of the 5-hydroxytryptamine(1A) receptor antagonist WAY100635 suppresses acute experimental allergic encephalomyelitis in Lewis rats.

Experimental allergic encephalomyelitis (EAE) is a T-cell inflammatory disease of the central nervous system (CNS) widely considered as an animal model of multiple sclerosis. In Lewis rats, myelin basic protein-complete Freund's adjuvant (MBP-CFA)-induced EAE is an acute monophasic disease from which animals recover fully. In our experiments, daily treatment (since day 1 after MBP-CFA inoculation) with the 5-hydroxytryptamine((1A)) (5-HT(1A)) receptor agonist (R)-(+)-8-hydroxy-2-(Dipropylamino)-tetralin (R(+)-8-OH-DPAT) resulted in a dose-related enhancement of neurological and histological signs in EAE-induced rats.

Effects of fluoxetine on the activity of phagocytosis in stressed mice.

We studied the effects of 1, 2, 5, 10 and 20 mg/kg of fluoxetine on the activity of phagocytosis in mice subjected to a chronic auditory stressor. Both the in vitro and in vivo activity of phagocytosis, measured using the zymosan-particle uptake method and the carbon clearance test, respectively, were reduced after 2, 4, 8 and 16 days of stress exposure. A partial recovery on the in vivo activity of phagocytosis was found on day 16th.

Effects of nefazodone on voluntary ethanol consumption induced by isolation stress in young and aged rats.

Late-onset ethanol (EtOH) consumption is related to life and social stressors of aging. The stress system (hypothalamic-pituitary-adrenal, HPA, axis) coordinates the adaptive response of the organism to stressors, but age-related deficits in HPA function seem to be associated with disorders such as late-onset EtOH consumption, anxiety and depression. In the present study, we examined whether HPA dysfunction is associated with stress-related EtOH consumption in aged rats and whether the treatment with nefazodone hydrochloride, a phenylpiperazine antidepressant, partially reverses the adverse effects of isolation (ISOL) stress.

Effects of psychological stress and alprazolam on development of oral candidiasis in rats.

Psychological stress has been found to suppress cell-mediated immune responses that are important in limiting the proliferation of Candida albicans. Since anxiolytic drugs can restore cellular immunity in rodents exposed to stress conditions, we designed experiments conducted to evaluate the effects of alprazolam (1 mg/kg of body weight/day), a central benzodiazepine anxiolytic agonist, on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C.

Music, immunity and cancer.

The effects of music on the immune system and cancer development were evaluated in rodents subjected to sound stress. Animals were exposed daily to broad band noise around midnight and/or music for 5 hours on the following morning. Thymus and spleen cellularity, peripheral T lymphocyte population, the proliferative response of spleen cells to mitogen concanavalin A and natural killer cell activity were calculated in BALB/c mice.