Fucoxanthin and Rosmarinic Acid Combination Has Anti-Inflammatory Effects through Regulation of NLRP3 Inflammasome in UVB-Exposed HaCaT Keratinocytes

Excessive exposure to ultraviolet (UV) radiation is the main risk factor to develop skin pathologies or cancer because it encourages oxidative condition and skin inflammation. In this sense, strategies for its prevention are currently being evaluated. Natural products such as carotenoids or polyphenols, which are abundant in the marine environment, have been used in the prevention of oxidative stress due to their demonstrated antioxidant activities. Nevertheless, the anti-inflammatory activity and its implication in photo-prevention have not been extensively studied. Thus, we aimed to evaluate the combination of fucoxanthin (FX) and rosmarinic acid (RA) on cell viability, apoptosis induction, inflammasome regulation, and anti-oxidative response activation in UVB-irradiated HaCaT keratinocytes. We demonstrated for the first time that the combination of FX and RA (5 µM RA plus 5 µM FX, designated as M2) improved antioxidant and anti-inflammatory profiles in comparison to compounds assayed individually, by reducing UVB-induced apoptosis and the consequent ROS production. Furthermore, the M2 combination modulated the inflammatory response through down-regulation of inflammasome components such as NLRP3, ASC, and Caspase-1, and the interleukin (IL)-1β production. In addition, Nrf2 and HO-1 antioxidant genes expression increased in UVB-exposed HaCaT cells pre-treated with M2. These results suggest that this combination of natural products exerts photo-protective effects by down-regulating NRLP3-inflammasome and increasing Nrf2 signalling pathway.Junta de Andalucía, Consejería de Innovación, Ciencia y Empresa-POLFANAT-P12-AGR-430Portugal, Fundação para a Ciência e a Tecnologia (FCT)-CESAM-UID/AMB/50017/2019Portugal, Fundação para a Ciência e a Tecnologia (FCT)-CEECIND/04050/2017Universidad de Sevilla "V Plan Propio US-PPI2015-1.5"

New Eunicellin-Type Diterpenes from the Panamanian Octocoral Briareum Asbestinum

Gorgonian octocorals are considered a prolific source of secondary metabolites with a wide range of biological activities, including anti-inflammatory activity. In particular, the genus Briareum is known for producing a wealth of diterpenes with complex chemical structures. The chemical study of the methanolic extract of Briareum asbestinum collected in Bocas del Toro, on the Caribbean side of Panama, led to the isolation of three new eunicellin-type diterpenes: briarellin T (1), asbestinin 27 (2), asbestinin 28 (3) and the previously described asbestinin 17 (4). The structures of the new compounds were determined by extensive NMR analyses and HRMS. Anti-inflammatory activity assays showed a significant reduction of the pro-inflammatory cytokines TNF-α, IL-6, IL-1β and IL-8 as well as a downregulation of COX-2 expression in LPS-stimulated THP-1 macrophages. These findings support the potential use of these marine compounds as therapeutic agents in the treatment of inflammatory diseases

Biological activity studies on marine natural products as therapeutic strategies in in vitro models of inflammation and colon cancer

Motivation: The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, it is the cause of several diseases, including cancer. Marine invertebrates are exceptional sources of new natural products, such as terpenoids, which are secondary metabolites that can exhibit anti-inflammatory and anticancerogenic activities. Colon cancer is a disease with a high genetic factor in which inflammation, and therefore its mediators, play an important role.This study focuses on the analysis of the biological activity of various natural terpenoids isolated from marine corals.Methods:HT-29 cells (human adenocarcinoma colon cell line) were grown in McCoy´s 5A and THP-1 cells (human monocytic leukemia cell line) in RPMI1640, both supplemented with 10% FBS and Strep/Pen (37ºC in 5% CO2 atmosphere). Cytotoxic activity was evaluated with the sulforhodamine (SRB) assay. The anti-inflammatory activity was tested on THP-1 through quantification of TNF-alpha, IL-6, IL-8, IL-1B and IL-10 by ELISA and COX-2 and iNOS levels by western-blot. Adherent macrophages were treated with terpenoids (10, 20 and 50 µM) for 1h, followed by stimulation of 1μg/mL LPS for 24h in both assays. Antioxidant activity was measured by ABTS assay.Results: Terpenes showed a moderate cytotoxic activity in both HT-29 and THP-1 macrophages after 48 and 72h. Pre-treatment with these compounds significantly reduced LPS-stimulated cytokines production in THP-1 cells as well as attenuated LPS-induced COX-2 and iNOS protein expression after 24 h. In addition, ABTS assay showed a low antioxidant activity.Conclusions: The five terpenes present a moderate antioxidant and cytotoxic activity as well as a potent anti-inflammatory effect in vitro. This kind of marine natural products may represent an interesting alternative for the treatment of inflammation-related diseases or cancer

Informalidad laboral y migración venezolana en el caribe colombiano. Percepciones de los vendedores de Cartagena de Indias y Santa Marta

This article analyzes the political conjuncture produced because of the Venezuelan migratory movement towards Colombia and other countries in the region and how the socioeconomic effects of their insertion into the informal economy are perceived by local non-formalized Colombian workers from the cities of Cartagena and Santa Marta, in the Colombian Caribbean. Methodologically, the article is descriptive. An analysis was conducted by reviewing documents and statistics sourced from the official archives which portray the dynamic landscape of Venezuelan migration. Furthermore, questionnaires were applied to a representative sample of informal merchants —stationary, semi-stationary, and itinerant— using the survey technique, to inquire about their socioeconomic characteristics, the knowledge they have about the arrival of new merchants due to the economic crisis in Venezuela, and their perceptions of the impact that occurred in the development of their commercial activities. Likewise, the actions and strategies that these subjects have taken to mitigate the effects of the insertion of migrants are determined.El presente artículo analiza la coyuntura política que produjo el movimiento migratorio venezolano hacia Colombia y otros países de la región y cómo los efectos socioeconómicos de su inserción en la economía informal son percibidos por los trabajadores locales colombianos no formalizados de las ciudades de Cartagena y Santa Marta, en el Caribe colombiano. Este artículo es de carácter descriptivo y recurrió metodológicamente a la revisión de documentos y estadísticas de los archivos oficiales, que recogen las dinámicas de la migración venezolana; asimismo, se aplicaron cuestionarios, mediante la técnica de encuesta, a una muestra representativa de vendedores informales —estacionarios, semi-estacionarios y ambulantes—, con el fin de indagar sobre sus características socioeconómicas, el conocimiento que tienen sobre la llegada de nuevos vendedores por la crisis económica de Venezuela y sus percepciones sobre la afectación que se produjo en el desarrollo de sus actividades comerciales. Del mismo modo, se determinan las acciones o estrategias que estos vendedores han tomado para mitigar los efectos de la inserción de migrantes

Effectiveness of pelvic floor muscle training in treating urinary incontinence in women: A current review.

OBJECTIVE: To analyse the content of various published studies related to physical exercise and its effects on urinary incontinence and to determine the effectiveness of pelvic floor training programmes. METHOD: We conducted a search in the databases of PubMed, CINAHL, the Cochrane Plus Library, The Cochrane Library, WOS and SPORTDiscus and a manual search in the Google Scholar metasearcher using the search descriptors for documents published in the last 10 years in Spanish or English. The documents needed to have an abstract or complete text on the treatment of urinary incontinence in female athletes and in women in general. RESULTS: We selected 3 full-text articles on treating urinary incontinence in female athletes and 6 full-text articles and 1 abstract on treating urinary incontinence in women in general. The 9 studies included in the review achieved positive results, i.e., there was improvement in the disease in all of the studies. CONCLUSIONS: Physical exercise, specifically pelvic floor muscle training programmes, has positive effects on urinary incontinence. This type of training has been shown to be an effective programme for treating urinary incontinence, especially stress urinary incontinence.Actividad Física y Deport

Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation

Anti-inflammatory effects of an oxylipin-containing lyophilised biomass from a microalga in a murine recurrent colitis model

Diet and nutritional factors have emerged as possible interventions for inflammatory bowel diseases (IBD), which are characterised by chronic uncontrolled inflammation of the intestinal mucosa. Microalgal species are a promising source of n-3 PUFA and derived oxylipins, which are lipid mediators with a key role in the resolution of inflammation. The aim of the present study was to investigate the effects of an oxylipin-containing lyophilised biomass from Chlamydomonas debaryana on a recurrent 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis mice model. Moderate chronic inflammation of the colon was induced in BALB/c mice by weekly intracolonic instillations of low dose of TNBS. Administration of the lyophilised microalgal biomass started 2 weeks before colitis induction and was continued throughout colitis development. Mice were killed 48 h after the last TNBS challenge. Oral administration of the microalgal biomass reduced TNBS-induced intestinal inflammation, evidenced by an inhibition of body weight loss, an improvement in colon morphology and a decrease in pro-inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-17. This product also down-regulated colonic expressions of inducible nitric oxide, cyclo-oxygenase 2 and NF-κB, as well as increased PPAR-γ. In addition, lyophilised microalgal biomass up-regulated the expressions of the antioxidant transcription factor nuclear factor E2-related factor 2 and the target gene heme oxygenase 1. This study describes for the first time the prophylactic effects of an oxylipin-containing lyophilised microalgae biomass from C. debaryana in the acute phase of a recurrent TNBS-induced colitis model in mice. These findings suggest the potential use of this microalga, or derived oxylipins, as a nutraceutical in the treatment of IBD.España Ministerio de Economía y Competitividad MICIIN PSE-0632/0151España MICIIN INNPACTO-IPT-2012-1370-060000

Anti-inflammatory and anticancer effects of microalgal carotenoids

Acute inflammation is a key component of the immune system's response to pathogens, toxic agents, or tissue injury, involving the stimulation of defense mechanisms aimed to removing pathogenic factors and restoring tissue homeostasis. However, uncontrolled acute inflammatory response may lead to chronic inflammation, which is involved in the development of many diseases, including cancer. Nowadays, the need to find new potential therapeutic compounds has raised the worldwide scientific interest to study the marine environment. Specifically, microalgae are considered rich sources of bioactive molecules, such as carotenoids, which are natural isoprenoid pigments with important beneficial effects for health due to their biological activities. Carotenoids are essential nutrients for mammals, but they are unable to synthesize them; instead, a dietary intake of these compounds is required. Carotenoids are classified as carotenes (hydrocarbon carotenoids), such as a- and |3 -carotene, and xanthophylls (oxygenate derivatives) including zeaxanthin, astaxanthin, fucoxanthin, lutein, a- and 3-cryptoxanthin, and canthaxanthin. This review summarizes the present up-to-date knowledge of the anti-inflammatory and anticancer activities of microalgal carotenoids both in vitro and in vivo, as well as the latest status of human studies for their potential use in prevention and treatment of inflammatory diseases and cancer.Universidad de Sevilla 2021/0000019

Up-Regulation of the Nrf2/HO-1 Antioxidant Pathway in Macrophages by an Extract from a New Halophilic Archaea Isolated in Odiel Saltworks

The production of reactive oxygen species (ROS) plays an important role in the progression of many inflammatory diseases. The search for antioxidants with the ability for scavenging free radicals from the body cells that reduce oxidative damage is essential to prevent and treat these pathologies. Haloarchaea are extremely halophilic microorganisms that inhabit hypersaline environments, such as saltworks or salt lakes, where they have to tolerate high salinity, and elevated ultraviolet (UV) and infrared radiations. To cope with these extreme conditions, haloarchaea have developed singular mechanisms to maintain an osmotic balance with the medium, and are endowed with unique compounds, not found in other species, with bioactive properties that have not been fully explored. This study aims to assess the potential of haloarchaea as a new source of natural antioxidant and anti-inflammatory agents. A carotenoid-producing haloarchaea was isolated from Odiel Saltworks (OS) and identified on the basis of its 16S rRNA coding gene sequence as a new strain belonging to the genus Haloarcula. The Haloarcula sp. OS acetone extract (HAE) obtained from the biomass contained bacterioruberin and mainly C18 fatty acids, and showed potent antioxidant capacity using ABTS assay. This study further demonstrates, for the first time, that pretreatment with HAE of lipopolysaccharide (LPS)-stimulated macrophages results in a reduction in ROS production, a decrease in the pro-inflammatory cytokines TNF-α and IL-6 levels, and up-regulation of the factor Nrf2 and its target gene heme oxygenase-1 (HO-1), supporting the potential of the HAE as a therapeutic agent in the treatment of oxidative stress-related inflammatory diseases.This research was funded by the Operative FEDER Program-Andalucía 2014-2020 (US-1380844 and UHU-1257518), Spanish Agencia Estatal de Investigación (PID2019-110438RBC22-AEI/FEDER), the Andalusian government (I+D+i-JA-PAIDI-Retos projects 2020-PY20) and the “VII Plan Propio de Investigación y Transferencia” of The University of Seville. The work was partially funded by national funds from Fundação para a Ciência e a Tecnologia (FCT, Portugal) in the scope of the projects UIDB/04565/2020 and UIDP/04565/2020 of the Research Unit iBB-Institute for Bioengineering and Biosciences, and of the project LA/P/0140/2020 of the i4HB-Associate Laboratory Institute for Health and Bioeconomy. P.G.-V acknowledges financial support from the “Margarita Salas” grant for the training of young doctors, University of Huelva

Dissociable Effects of Executive Load on Perceived Exertion and Emotional Valence during Submaximal Cycling

Endurance physical exercise is accompanied by subjective perceptions of exertion (reported perceived exertion, RPE), emotional valence, and arousal. These constructs have been hypothesized to serve as the basis for the exerciser to make decisions regarding when to stop, how to regulate pace, and whether or not to exercise again. In dual physical-cognitive tasks, the mental (executive) workload generated by the cognitive task has been shown to influence these perceptions, in ways that could also influence exercise-related decisions. In the present work, we intend to replicate and extend previous findings that manipulating the amount of executive load imposed by a mental task, performed concomitantly with a submaximal cycling session, influenced emotional states but not perceived exertion. Participants (experienced triathletes) were asked to perform a submaximal cycling task in two conditions with different executive demands (a two-back version of the n-back task vs. oddball) but equated in external physical load. Results showed that the higher executive load condition elicited more arousal and less positive valence than the lower load condition. However, both conditions did not differ in RPE. This experimental dissociation suggests that perceived exertion and its emotional correlates are not interchangeable, which opens the possibility that they could play different roles in exercise-related decision-making.Spanish Ministry of Economy and Competitiveness (Secretaria de Estado de Investigacion, Desarrollo e Innovacion; Convocatoria 2017 de Proyectos I + D, de Retos a la Sociedad; Spain) DEP2017-89879-RSpanish Government (Ministerio de Economia y Competitividad, Secretaria de Estado de Investigacion, Desarrollo e Innovacion; Convocatoria 2017 de Proyectos I + D de Excelencia, Spain - Fondo Europeo de Desarrollo Regional, FEDER, European Union) PSI2017-85488-