Potential of Oral Nanoparticles Containing Cytokines as Intestinal Mucosal Immunostimulants in Pigs : A Pilot Study

Antibiotics are essential compounds to cope with bacterial infections. However, their inadequate and excessive use has triggered the rapid arising of antimicrobial-resistant bacteria. In this scenario, immunostimulants, which are molecules that boost the immune system, open up a new approach to face this problem, enhancing treatment efficacy and preventing infections by immune system response. Cytokines are central effector molecules of the immune system, and their recombinant production and administration in animals could be an interesting immune modulation strategy. The aim of this study was the development of a highly stable nanoparticle of porcine cytokines to achieve the immunostimulation of intestinal mucosa in piglets. The outcomes of the present study prove this approach is able to stimulate swine intestinal cells and macrophages in vitro and tends to modulate inflammatory responses in vivo, although further studies are required to definitively evaluate their potential in animals. Antimicrobial resistance is a global threat that is worryingly rising in the livestock sector. Among the proposed strategies, immunostimulant development appears an interesting approach to increase animal resilience at critical production points. The use of nanoparticles based on cytokine aggregates, called inclusion bodies (IBs), has been demonstrated as a new source of immunostimulants in aquaculture. Aiming to go a step further, the objective of this study was to produce cytokine nanoparticles using a food-grade microorganism and to test their applicability to stimulate intestinal mucosa in swine. Four cytokines (IL-1β, IL-6, IL-8, and TNF-α) involved in inflammatory response were produced recombinantly in Lactococcus lactis in the form of protein nanoparticles (IBs). They were able to stimulate inflammatory responses in a porcine enterocyte cell line (IPEC-J2) and alveolar macrophages, maintaining high stability at low pH and high temperature. In addition, an in vivo assay was conducted involving 20 piglets housed individually as a preliminary exploration of the potential effects of IL-1β nanoparticles in piglet intestinal mucosa after a 7 d oral administration. The treated animals tended to have greater levels of TNF-α in the blood, indicating that the tested dose of nanoparticles tended to generate an inflammatory response in the animals. Whether this response is sufficient to increase animal resilience needs further evaluation

In Vivo Evaluation of 3-Dimensional Polycaprolactone Scaffolds for Cartilage Repair in Rabbits

Background: Cartilage tissue engineering using synthetic scaffolds allows maintaining mechanical integrity and withstanding stress loads in the body, as well as providing a temporary substrate to which transplanted cells can adhere. Purpose: This study evaluates the use of polycaprolactone (PCL) scaffolds for the regeneration of articular cartilage in a rabbit model. Study Design: Controlled laboratory study. Methods: Five conditions were tested to attempt cartilage repair. To compare spontaneous healing (from subchondral plate bleeding) and healing due to tissue engineering, the experiment considered the use of osteochondral defects (to allow blood flow into the defect site) alone or filled with bare PCL scaffold and the use of PCL-chondrocytes constructs in chondral defects. For the latter condition, 1 series of PCL scaffolds was seeded in vitro with rabbit chondrocytes for 7 days and the cell/scaffold constructs were transplanted into rabbits’ articular defects, avoiding compromising the subchondral bone. Cell pellets and bare scaffolds were implanted as controls in a chondral defect. Results: After 3 months with PCL scaffolds or cells/PCL constructs, defects were filled with white cartilaginous tissue; integration into the surrounding native cartilage was much better than control (cell pellet). The engineered constructs showed histologically good integration to the subchondral bone and surrounding cartilage with accumulation of extracellular matrix including type II collagen and glycosaminoglycan. The elastic modulus measured in the zone of the defect with the PCL/cells constructs was very similar to that of native cartilage, while that of the pellet-repaired cartilage was much smaller than native cartilage. Conclusion: The results are quite promising with respect to the use of PCL scaffolds as aids for the regeneration of articular cartilage using tissue engineering techniques.The support of the Spanish Ministry of Science through projects No. MAT2007-66759-C03-01 and MAT2007-66759C03-02 (including FEDER financial support) is acknowledged. Dr Gomez Tejedor acknowledges the support given by the government of Valencia, the Generalitat Valenciana, through the GVPRE/2008/160 project. The support of Grant 2005SGR 00762 and 2005SGR 00848 (Catalan Department of Universities, Research and the Information Society) is also acknowledged. The Aging and Fragile Elderly cooperative research network (Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad [RETICEF]) and the Bioengineering, Biomaterials and Nanomedicine research network (Centro de Investigacion Biomedica en Red en Bioingenieria, Biomateriales y Nanomedicina [CIBER BBN]) are initiatives of the Instituto de Salud Carlos III (ISCIII). The group of the Centro de Investigacion Principe Felipe (CIPF) acknowledges funding in the framework of the collaboration agreement among the ISCIII, the Conselleria de Sanidad de la Comunidad Valenciana, and the CIPF for the "Investigacion Basica y Traslacional en Medicina Regenerativa."Martinez-Diaz, S.; Garcia-Giralt, N.; Lebourg, MM.; Gómez-Tejedor, JA.; Vila, G.; Caceres, E.; Benito, P.... (2010). In Vivo Evaluation of 3-Dimensional Polycaprolactone Scaffolds for Cartilage Repair in Rabbits. American Journal of Sports Medicine. 38(3):509-519. https://doi.org/10.1177/0363546509352448S50951938

Spanish consensus document on diagnosis, stabilisation and treatment of pediatric multisystem inflammatory syndrome related to SARS-CoV-2 (SIM-PedS)

A new paediatric multisystem inflammatory syndrome, linked to SARS-CoV-2, has been described. The clinical picture is variable and is associated with an active or recent infection due to SARS-CoV-2. A review of the existing literature by a multidisciplinary group of paediatric specialists is presented in this document. Later, they make recommendations on the stabilisation, diagnosis, and treatment of this syndrome.YesSe ha descrito un nuevo síndrome inflamatorio multisistémico pediátrico vinculado a SARS-CoV-2. Este cuadro presenta una expresividad clínica variable y se asocia a infección activa o reciente por SARS-CoV-2. En este documento se revisa la literatura existente por parte de un grupo multidisciplinar de especialistas pediátricos. Posteriormente, se realizan recomendaciones sobre estabilización, diagnóstico y tratamiento de este síndrome

Documento español de consenso sobre diagnóstico, estabilización y tratamiento del síndrome inflamatorio multisistémico pediátrico vinculado a SARS-CoV-2 (SIM-PedS).

A new paediatric multisystem inflammatory syndrome, linked to SARS-CoV-2, has been described. The clinical picture is variable and is associated with an active or recent infection due to SARS-CoV-2. A review of the existing literature by a multidisciplinary group of paediatric specialists is presented in this document. Later, they make recommendations on the stabilisation, diagnosis, and treatment of this syndrome

PATJ low frequency variants are associated with worse ischemic stroke functional outcome: a genome-wide meta-analysis

Rationale: Ischemic stroke (IS) is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. Objective: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest genome-wide association study (GWAS) in IS recovery to date. Methods and Results: A 12-cohort, two-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent IS cases. Functional outcome was recorded using 3-month modified Rankin Scale (mRS). Analyses were adjusted for confounders such as discharge NIHSS. A gene-based burden test was performed. The discovery phase (n=1,225) was followed by open (n=2,482) and stringent joint-analyses (n=1,791). Those cohorts with mRS recorded at timepoints other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, beta=0·40, p=1·70x10-9). Conclusions: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci