Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris

IntroductionThe involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms.MethodsWe performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions.ResultsThe results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses.ConclusionsThese data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases

Construyendo soberanía alimentaria en el barrio: forjando futuro : Algunas reflexiones a partir de la actividad extensionista

Desde el equipo interdisciplinario compuesto por integrantes de las Facultades de Trabajo Social, Ciencias Naturales y Museo, Ciencias Exactas y Periodismo y Comunicación Social de la UNLP, se ha generado un espacio de construcción de diálogo de saberes adecuados para la realización sistemática de acciones de capacitación, tendientes a formar en temas vinculados con la agro-ecología, la soberanía y la seguridad alimentaria, a aquellas personas que viven en situación de vulnerabilidad y exclusión, y que muchas veces ven agudizadas las problemáticas habituales por situaciones adversas vinculadas con catástrofes naturales (como las inundaciones del 2 de abril de 2013 u otras), cambio climático, etc. Este proyecto de extensión se ha articulado con la Coordinadora de Trabajadores Desocupados "Aníbal Verón” y la Comunidad Boliviana del barrio "El Futuro” del Gran La Plata. En este proyecto nos propusimos realizar acciones con la Coordinadora de Trabajadores Desocupados "Aníbal Verón”, el Movimiento Justicia y Libertad y la Comunidad Boliviana del barrio "El Futuro” del Gran La Plata. Se destaca que las organizaciones mencionadas vienen formando parte del Consejo Social de la UNLP, articulando acciones en distintas temáticas, en especial en cuestiones que dan origen y experiencia al presente proyecto. Se realizaron talleres periódicos orientados a consolidar prácticas agrícolas y hortícolas sustentables témporo-espacialmente, generando respuestas ante la creciente demanda que reclama la obtención de alimentos sanos y a bajo costo, en el marco de una economía social que se pretende solidaria, a escala humana, y que promueve una fuente de insumos y de trabajo en un contexto donde se privilegie el comercio justo. La misma dinámica del Proyecto llevó a que otras instituciones del Barrio que no estaban contempladas inicialmente, se incorporen al mismo como, es el caso de la Sala de Atención Primaria de la Salud. La problemáticas tratadas se vinculan con la necesidad de generar una formación sistemática y permanente sobre la nutrición, la producción y calidad de los alimentos, la soberanía y seguridad alimentaria, la manipulación y el impacto en la salud de los alimentos y la disponibilidad alimentaria en nuestro país, apuntando a favorecer estrategias de producción y obtención de alimentos sobre la base de una agricultura familiar desde una perspectiva agroecológica.Eje 2: Debates sobre el Trabajo Social y las ciencias sociales: su implicancia en el contexto actual.Facultad de Trabajo Socia

Construyendo soberanía alimentaria en el barrio: forjando futuro : Algunas reflexiones a partir de la actividad extensionista

Desde el equipo interdisciplinario compuesto por integrantes de las Facultades de Trabajo Social, Ciencias Naturales y Museo, Ciencias Exactas y Periodismo y Comunicación Social de la UNLP, se ha generado un espacio de construcción de diálogo de saberes adecuados para la realización sistemática de acciones de capacitación, tendientes a formar en temas vinculados con la agro-ecología, la soberanía y la seguridad alimentaria, a aquellas personas que viven en situación de vulnerabilidad y exclusión, y que muchas veces ven agudizadas las problemáticas habituales por situaciones adversas vinculadas con catástrofes naturales (como las inundaciones del 2 de abril de 2013 u otras), cambio climático, etc. Este proyecto de extensión se ha articulado con la Coordinadora de Trabajadores Desocupados "Aníbal Verón” y la Comunidad Boliviana del barrio "El Futuro” del Gran La Plata. En este proyecto nos propusimos realizar acciones con la Coordinadora de Trabajadores Desocupados "Aníbal Verón”, el Movimiento Justicia y Libertad y la Comunidad Boliviana del barrio "El Futuro” del Gran La Plata. Se destaca que las organizaciones mencionadas vienen formando parte del Consejo Social de la UNLP, articulando acciones en distintas temáticas, en especial en cuestiones que dan origen y experiencia al presente proyecto. Se realizaron talleres periódicos orientados a consolidar prácticas agrícolas y hortícolas sustentables témporo-espacialmente, generando respuestas ante la creciente demanda que reclama la obtención de alimentos sanos y a bajo costo, en el marco de una economía social que se pretende solidaria, a escala humana, y que promueve una fuente de insumos y de trabajo en un contexto donde se privilegie el comercio justo. La misma dinámica del Proyecto llevó a que otras instituciones del Barrio que no estaban contempladas inicialmente, se incorporen al mismo como, es el caso de la Sala de Atención Primaria de la Salud. La problemáticas tratadas se vinculan con la necesidad de generar una formación sistemática y permanente sobre la nutrición, la producción y calidad de los alimentos, la soberanía y seguridad alimentaria, la manipulación y el impacto en la salud de los alimentos y la disponibilidad alimentaria en nuestro país, apuntando a favorecer estrategias de producción y obtención de alimentos sobre la base de una agricultura familiar desde una perspectiva agroecológica.Eje 2: Debates sobre el Trabajo Social y las ciencias sociales: su implicancia en el contexto actual.Facultad de Trabajo Socia

p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis

Genome organizer Satb1 is regulated by p63 and contributes to epidermal morphogenesis by remodeling chromatin structure and gene expression at the epidermal differentiation complex locus

The Role of BPIFB4 in Immune System and Cardiovascular Disease: The Lesson from Centenarians

: Recent discoveries have shed light on the participation of the immune system in the physio pathology of the cardiovascular system underpinning the importance of keeping the balance of the first to preserve the latter. Aging, along with other risk factors, can challenge such balance triggering the onset of cardiovascular diseases. Among several mediators ensuring the proper cross-talk between the two systems, bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) has been shown to have a pivotal role, also by sustaining important signals such as eNOS and PKC-alpha. In addition, the Longevity-associated variant (LAV), which is an haplotype allele in BPIFB4 characterized by 4 missense polymorphisms, enriched in homozygosity in Long Living Individuals (LLIs), has been shown to be efficient, if administered systemically through gene therapy, in improving many aspects of cardiovascular diseases (CVDs). This occurs mainly through a fine immune system remodeling across: 1) a M2 macrophage polarizing effect, 2) a favorable redistribution of the circulating monocyte cell subsets and 3) the reduction of T-cell activation. Furthermore, LAV-BPIFB4 treatment induced a desirable recovery of the inflammatory balance by mitigating the pro-inflammatory factor levels and enhancing the anti-inflammatory boost through a mechanism that is partially dependent on SDF-1/CXCR4 axis. Importantly, the remarkable effects of LAV-BPIFB4 treatment, which translates in increased BPIFB4 circulating levels, mirror what occurs in long-living individuals (LLIs) in whom the high circulating levels of BPIFB4 are protective from age-related and CVDs and emphasize the reason why LLIs are considered a model of successful aging. Here, we review the mechanisms by which LAV-BPIFB4 exerts its immunomodulatory activity in improving the cardiovascular-immune system dialogue that might strengthen its role as a key mediator in CVDs

Klebsiella pneumoniae-OMVs activate death-signaling pathways in Human Bronchial Epithelial Host Cells (BEAS-2B)

The programmed cell death pathways of apoptosis are important in mammalian cellular protection from infections. The activation of these pathways depends on the presence of membrane receptors that bind bacterial components to activate the transduction mechanism. In addition to bacteria, these mechanisms can be activated by outer membrane vesicles (OMVs). OMVs are spherical vesicles of 20–250 nm diameter, constitutively released by Gram-negative bacteria. They contain several bacterial determinants including proteins, DNA/RNA and proteins, that activate different cellular processes in host cells. This study focused on Klebsiella pneumoniae-OMVs in activating death mechanisms in human bronchial epithelial cells (BEAS-2B). Characterization of purified OMVs was achieved by scanning electron microscopy, nanoparticle tracking analysis and protein profiling. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while apoptotic induction was measured by flow cytometry and confirmed by western blotting. The OMVs produced showed a spherical morphology, with a diameter of 137.2 ± 41 nm and a vesicular density of 7.8 × 109 particles/mL Exposure of cell monolayers to 50 μg of K. pneumoniae-OMV for 14 h resulted in approximately 25 % cytotoxicity and 41.15–41.14 % of cells undergoing early and late apoptosis. Fluorescence microscopy revealed reduced cellular density, the presence of apoptotic bodies, chromatin condensation, and nuclear membrane blebbing in residual cells. Activation of caspases −3 and −9 and dysregulation of BAX, BIM and Bcl-xL indicated the activation of mitochondria-dependent apoptosis. Furthermore, a decrease in the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase involved endoplasmic reticulum stress with the potential formation of reactive oxygen species. These findings provide evidence for the role of OMVs in apoptosis and involvement in the pathogenesis of K. pneumoniae infections

Gender Differences Associated with the Prognostic Value of BPIFB4 in COVID-19 Patients: A Single-Center Preliminary Study

In the ongoing global COVID-19 pandemic, male sex is a risk factor for severe disease and death, and the reasons for these clinical discrepancies are largely unknown. The aim of this work is to study the influence of sex on the course of infection and the differences in prognostic markers between genders in COVID-19 patients. Our cohort consisted of 64 adult patients (n = 34 men and n = 30 women) with PCR-proven SARS-CoV-2 infection. Further, a group of patients was characterized by a different severity degree (n = 8 high- and n = 8 low-grade individuals for both male and female patients). As expected, the serum concentrations of LDH, fibrinogen, CRP, and leucocyte count in men were significantly higher than in females. When serum concentrations of the inflammatory cytokines, including IL-6, IL-2, IP-10 and IL-4 and chemokines like MCP-1, were measured with multiplex ELISA, no significant differences between male and female patients were found. In COVID-19 patients, we recently attributed a new prognostic value to BPIFB4, a natural defensin against dysregulation of the immune responses. Here, we clarify that BPIFB4 is inversely related to the disease degree in men but not in women. Indeed, higher levels of BPIFB4 characterized low-grade male patients compared to high-grade ones. On the contrary, no significant difference was reported between low-grade female patients and high-grade ones. In conclusion, the identification of BPIFB4 as a biomarker of mild/moderate disease and its sex-specific activity would open an interesting field for research to underpin gender-related susceptibility to the disease

SARS-CoV-2 Lysate Stimulation Impairs the Release of Platelet-like Particles and Megakaryopoiesis in the MEG-01 Cell Line

SARS-CoV-2 infection causes a considerable inflammatory response coupled with impaired platelet reactivity, which can lead to platelet disorders recognized as negative prognostic factors in COVID-19 patients. The virus may cause thrombocytopenia or thrombocytosis during the different disease stages by destroying or activating platelets and influencing platelet production. While it is known that several viruses can impair megakaryopoiesis by generating an improper production and activation of platelets, the potential involvement of SARS-CoV-2 in affecting megakaryopoiesis is poorly understood. To this purpose, we explored, in vitro, the impact of SARS-CoV-2 stimulation in the MEG-01 cell line, a human megakaryoblastic leukemia cell line, considering its spontaneous capacity of releasing platelet-like particles (PLPs). We interrogated the effect of heat-inactivated SARS-CoV-2 lysate in the release of PLPs and activation from MEG-01, the signaling pathway influenced by SARS-CoV-2, and the functional effect on macrophagic skewing. The results highlight the potential influence of SARS-CoV-2 in the early stages of megakaryopoiesis by enhancing the production and activation of platelets, very likely due to the impairment of STATs signaling and AMPK activity. Overall, these findings provide new insight into the role of SARS-CoV-2 in affecting megakaryocyte-platelet compartment, possibly unlocking another avenue by which SARS-CoV-2 moves

Longevity-associated BPIFB4 gene counteracts the inflammatory signaling

Background: Increased levels of pro-inflammatory proteins in plasma can be detected in older individuals and associate with the so called chronic low-grade inflammation, which contributes to a faster progression of aged-related cardiovascular (CV) diseases, including frailty, neurodegeneration, gastro-intestinal diseases and disorders reflected by alterations in the composition of gut microbiota. However, successful genetic programme of long-living individuals alters the trajectory of the ageing process, by promoting an efficient immune response that can counterbalance deleterious effects of inflammation and the CV complications. This is the case of BPIFB4 gene in which, homozygosity for a four single-nucleotide polymorphism (SNP) haplotype, the Longevity-Associated Variant (LAV) correlates with prolonged health span and reduced risk of CV complications and inflammation. The relation between LAV-BPIFB4 and inflammation has been proven in different experimental models, here we hypothesized that also human homozygous carriers of LAV-BPIFB4 gene may experience a lower inflammatory burden as detected by plasma proteomics that could explain their favourable CV risk trajectory over time. Moreover, we explored the therapeutic effects of LAV-BPIFB4 in inflammatory disease and monolayer model of intestinal barrier. Results: We used high-throughput proteomic approach to explore the profiles of circulating proteins from 591 baseline participants selected from the PLIC cohort according to the BPIFB4 genotype to identify the signatures and differences of BPIFB4 genotypes useful for health and disease management. The observational analysis identified a panel of differentially expressed circulating proteins between the homozygous LAV-BPIFB4 carriers and the other alternative BPIFB4 genotypes highlighting in the latter ones a higher grade of immune-inflammatory markers. Moreover, in vitro studies performed on intestinal epithelial organs from inflammatory bowel disease (IBD) patients and monolayer model of intestinal barrier demonstrated the benefit of LAV-BPIFB4 treatment. Conclusions: Homozygosity for LAV-BPIFB4 results in the attenuation of inflammation in PLIC cohort and IBD patients providing preliminary evidences for its therapeutic use in inflammatory disorders that need to be further characterized and confirmed by independent studies