Potential Role of Seaweed Polyphenols in Cardiovascular-Associated Disorders

The beneficial effects of various polyphenols with plant origins on different cardiovascular-associated disorders, such as hypertension, diabetes mellitus type 2 and metabolic syndrome are well known. Recently, marine crude-drugs are emerging as potential treatments in many noncommunicable conditions, including those involving the cardiovascular system. Among the active compounds responsible for these activities, seaweed polyphenols seem to play a key role. The aim of the present review is to summarise the current knowledge about the beneficial effects reported for edible seaweed polyphenols in the amelioration of these prevalent conditions, focusing on both preclinical and clinical studies. This review will help to establish the basis for future studies in this promising field.This work was supported by the Junta de Andalucía (CTS 164) and by the Spanish Ministry of Economy and Competitiveness (AGL2015-67995-C3-3-R) with funds from the European Union. The CIBER-EHD is funded by the Instituto de Salud Carlos III

Limosilactobacillus fermentum CECT5716: Mechanisms and Therapeutic Insights

This work was supported by the Junta de Andalucía (CTS 164) and Instituto de Salud Carlos III (PI19/01058) with funds from the European Union.M.J. Rodríguez-Sojo is a predoctoral fellow from University of Granada (“Programa de Doctorado en Biomedicina”); A.J. Ruiz-Malagón is a predoctoral fellow from Formación de Profesorado Universitario Program (“Programa de Doctorado en Medicina Clínica y Salud Pública”), and A. Rodríguez-Nogales is a postdoctoral fellow of Instituto de Salud Carlos III (Miguel Servet Program).Probiotics microorganisms exert their health-associated activities through some of the following general actions: competitive exclusion, enhancement of intestinal barrier function, production of bacteriocins, improvement of altered microbiota, and modulation of the immune response. Among them, Limosilactobacillus fermentum CECT5716 has become one of the most promising probiotics and it has been described to possess potential beneficial effects on inflammatory processes and immunological alterations. Different studies, preclinical and clinical trials, have evidenced its anti-inflammatory and immunomodulatory properties and elucidated the precise mechanisms of action involved in its beneficial effects. Therefore, the aim of this review is to provide an updated overview of the effect on host health, mechanisms, and future therapeutic approaches.Junta de Andalucia CTS 164Instituto de Salud Carlos III European Commission PI19/01058European Commissio

Intestinal anti-inflammatory and visceral analgesic effects of a Serpylli herba extract in an experimental model of irritable bowel syndrome in rats

Ethnopharmacological relevance: Serpylli herba extract (SHE), composed of the aerial parts of wild thyme (Thymus serpyllum L.) (Lamiaceae family), is traditionally used in Europe and North Africa to treat diarrhea, gastric ulcers, intestinal parasites and upper respiratory tract infections. Recently, SHE has generated a great interest for irritable bowel syndrome (IBS) management, probably due to its intestinal anti-inflammatory properties shown in experimental colitis and the fact that its active components could preserve the intestinal barrier integrity, which is altered in patients with IBS. Aim of study: We aimed to test the effects of a SHE in a rat experimental model resembling human IBS. Materials and methods: IBS was provoked by deoxycholic acid (DCA). Rats were then treated with SHE (100 mg/kg) or gabapentin (70 mg/kg) and different inflammatory and gut barrier integrity markers were evaluated. Moreover, several gut hypersensitivity and hyperalgesia determinations were performed. Results: SHE improved referred pain and visceral hypersensitivity. Additionally, SHE enhanced immune status by downregulating of the expression of the proinflammatory mediators Il-1β, Il-6, Ifn-γ, Tlr-4, and the inducible enzyme Cox-2, thus inducing visceral analgesia, and promoting the restore of the gut barrier function by upregulating the mucins Muc-2 and Muc-3. These antiinflammatory effects could be related to its action on mast cells since it significantly inhibited the β-Hexosaminidase production in RBL-2H3 cells. Lastly, SHE also seems to modulate the serotonin pathway by restoring the altered expression of the 5-HT receptors Htr-3 and Htr-4. Conclusion: SHE could be considered a potential new treatment for IBS, since it ameliorates hypersensitivity, visceral hyperalgesia, and inflammation. These beneficial effects may be due to the inhibition of mast cells degranulation and serotonin pathway.Junta de Andalucia AGR6826 CTS 164Spanish Government SAF 2011-29648Instituto de Salud Carlos IIIEuropean Commission PI19/01058 PI20/0144

Novel Horizons in Postbiotics: Lactobacillaceae Extracellular Vesicles and Their Applications in Health and Disease

Lactobacillus probiotics contained in dietary supplements or functional foods are wellknown for their beneficial properties exerted on host health and diverse pathological situations. Their capacity to improve inflammatory bowel disease (IBD) and regulate the immune system is especially remarkable. Although bacteria–host interactions have been thought to occur directly, the key role that extracellular vesicles (EVs) derived from probiotics play on this point is being unveiled. EVs are lipid bilayer-enclosed particles that carry a wide range of cargo compounds and act in different signalling pathways. Notably, these EVs have been recently proposed as a safe alternative to the utilisation of live bacteria since they can avoid the possible risks that probiotics may entail in vulnerable cases such as immunocompromised patients. Therefore, this review aims to give an updated overview of the existing knowledge about EVs from different Lactobacillus strains, their mechanisms and effects in host health and different pathological conditions. All of the information collected suggests that EVs could be considered as potential tools for the development of future novel therapeutic approaches.Junta de Andalucia CTS 164 PY20_01157Instituto de Salud Carlos III European Commission PI19/01058 European Commissio

General Analysis of Switching Modes in a Dual Active Bridge with Triple Phase Shift Modulation

This paper provides an exhaustive analysis of the Dual-Active-Bridge with Triple-Phase-Shift (DAB-TPS) modulation and other simpler ones, identifying all the possible switching modes to operate the DAB in both power flow directions, and for any input-to-output voltage range and output power. This study shows four cases and seven switching modes for each case when the energy flows in one direction. That means that the DAB operates up to fifty-six different switching modes when the energy flows in both directions. Analytical expressions for the inductor current, the output power, and the boundaries between switching modes are provided for all cases. Additionally, the combination of control variables to achieve Zero-Voltage-Switching (ZVS) or Zero-Current-Switching (ZCS) is provided for each case and switching mode, by showing which switching modes obtain ZVS or ZCS for the whole power range and all switches—independent of the input-to-output voltage ratio. Therefore, the most interesting cases, switching mode and modulation for using the DAB are identified. Additionally, experimental validation has been carried out with a 250 W prototype. This analysis is a proper tool to design the DAB in the optimum switching mode, reducing the RMS current and achieving to increase efficiency and the power density.This research was funded by the Spanish Ministry of Economy and Competitiveness and ERDF, grant number DPI2014-53685-C2-1-R

Calcium Pyruvate Exerts Beneficial Effects in an Experimental Model of Irritable Bowel Disease Induced by DCA in Rats

Pyruvate is a normal constituent of the body that participates in carbohydrate metabolism and functions as a scavenger of free radicals. Calcium pyruvate monohydrate (CPM) is a more stable derivative that has proved its anti-inflammatory effect in experimental colitis, among other disorders, and that could also be considered a source of calcium. Thus, it would be useful for the treatment of diseases with an inflammatory component and a high prevalence of osteoporosis like the irritable bowel syndrome (IBS). The aim of the present study is to evaluate the effects of CPM in a rat model of chronic post-inflammatory visceral pain induced by deoxycholic acid (DCA) that resembles IBS. Rats were administered DCA for three days intracolonically and then treated daily with CPM (40 and 100 mg/kg) or gabapentin (70 mg/kg) (positive control) by oral gavage for 17 days. The treatments reduced the visceral hypersensitivity measured by response to colorectal distension and referred pain. DCA induced changes in the colonic immune response characterized by increased expression of the cytokine Il-1b and the inducible enzyme Cox-2, which was reduced by the treatments. DCA also decreased the gut expression of the mucins Muc-2 and Muc-3, which was normalized by CPM, whereas gabapentin only increased significantly Muc-3. Moreover, DCA increased the expression of Tlr3, which was decreased to basal levels by all the treatments. However, the serotonin receptor Htr-4, which was also elevated, was not affected by any of the treatments, indicating no effect through this signalling pathway. In conclusion, CPM ameliorated the visceral hypersensitivity and the referred pain caused by DCA, being as effective as the control drug. Furthermore, it improved the immune status of the animals, which could contribute to the visceral analgesia and the regeneration of the intestinal epithelial barrier integrity.This work was supported by the Junta de Andalucía (CTS 164) and by the Spanish Ministry of Economy and Competitiveness (AGL2015-67995-C3-3-R) with funds from the European Union. The CIBER-EHD is funded by the Instituto de Salud Carlos III

Tigecycline reduces tumorigenesis in colorectal cancer via inhibition of cell proliferation and modulation of immune response

Junta de Andalucía (CTS 164)Instituto de Salud Carlos III (Spain)Fondo Europeo de Desarrollo Regional (FEDER)European Union, through the research grants PI18/00826, P18-RT-4930, PI0206–2016, PIE16/00045 and PI19/01058Spanish Ministry of Science and Innovation (MCIN/AEI/ 10.13039/501100011033/FEDER)RTI2018–101309-BC22Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963Spanish Ministry of Science and Innovation (“Programa de Doctorado: Medicina Clínica y Salud Pública” B12.56.1).Instituto de Salud Carlos III (FI17/00176)Junta de Andalucía (P18-RT-4930)University of GranadaCIBER-EHD is funded by the Instituto de Salud Carlos II

Intestinal Anti-inflammatory Effects of Outer Membrane Vesicles from Escherichia coli Nissle 1917 in DSS-Experimental Colitis in Mice

Escherichia coli Nissle 1917 (EcN) is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not fully known. Gram-negative bacteria release outer membrane vesicles (OMVs) as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS)-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 mg/day) significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic-host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration. Keywords: probiotic, Escherichia coli Nissle 1917, outer membrane vesicles, DS

Bacteria-Carried Iron Oxide Nanoparticles for Treatment of Anemia

The efficiency of maghemite nanoparticles for the treatment of anemia was sensibly higher when nanoparticles were incorporated onto the probiotic bacterium Lactobacillus fermentum (MNP-bacteria) than when administrated as uncoated nanoparticles (MNP). Plasma iron and hemoglobin, intestine expression of divalent metal transporter 1 (DMT1) and duodenal Cytochrome b (DcytB), as well as hepatic expression of the hormone hepcidin were fully restored to healthy levels after administration of MNP-bacteria but not of MNP. A magnetic study on biodistribution and biodegradation showed accumulation of maghemite nanoparticles in intestine lumen when MNP-bacteria were administrated. In contrast, MNP barely reached intestine. In vivo MRI studies suggested the internalization of MNP-bacteria into enterocytes, which did not occur with MNP. Transmission electronic microscopy confirmed this internalization. The collective analysis of results point out that L. fermentum is an excellent carrier to overcome the stomach medium and drive maghemite nanoparticles to intestine, where iron absorption occurs. Due the probiotic ability to adhere to the gut wall, MNP-bacteria internalize into the enterocyte, where maghemite nanoparticles are delivered, providing an adequate iron level into enterocyte. This paper advances a new route for effective iron absorption in the treatment of anemia.The efficiency of maghemite nanoparticles for the treatment of anemia was sensibly higher when nanoparticles were incorporated onto the probiotic bacterium Lactobacillus fermentum (MNP-bacteria) than when administrated as uncoated nanoparticles (MNP). Plasma iron and hemoglobin, intestine expression of divalent metal transporter 1 (DMT1) and duodenal Cytochrome b (DcytB), as well as hepatic expression of the hormone hepcidin were fully restored to healthy levels after administration of MNP-bacteria but not of MNP. A magnetic study on biodistribution and biodegradation showed accumulation of maghemite nanoparticles in intestine lumen when MNP-bacteria were administrated. In contrast, MNP barely reached intestine. In vivo MRI studies suggested the internalization of MNP-bacteria into enterocytes, which did not occur with MNP. Transmission electronic microscopy confirmed this internalization. The collective analysis of results point out that L. fermentum is an excellent carrier to overcome the stomach medium and drive maghemite nanoparticles to intestine, where iron absorption occurs. Due the probiotic ability to adhere to the gut wall, MNP-bacteria internalize into the enterocyte, where maghemite nanoparticles are delivered, providing an adequate iron level into enterocyte. This paper advances a new route for effective iron absorption in the treatment of anemia

Vanadium Decreases Hepcidin mRNA Gene Expression in STZ-Induced Diabetic Rats, Improving the Anemic State

We are grateful for the support received from the Consejeria de Innovacion, Ciencia y Empresa, Andalusian Regional Government (Project P06-CTS-01435), and from the Spanish Ministry of Economy and Competitivity (SAF2011-29648); the CIBERehd is funded by the Instituto de Salud Carlos III.This paper forms part of the Doctoral Program in Nutrition and Food Science of the University of Granada.Diabetes is a disease with an inflammatory component that courses with an anemic state. Vanadium (V) is an antidiabetic agent that acts by stimulating insulin signaling. Hepcidin blocks the intestinal absorption of iron and the release of iron from its deposits. We aim to investigate the effect of V on hepcidin mRNA expression and its consequences on the hematological parameters in streptozotocin-induced diabetic Wistar rats. Control healthy rats, diabetic rats, and diabetic rats treated with 1 mgV/day were examined for five weeks. The mineral levels were measured in diet and serum samples. Hepcidin expression was quantified in liver samples. Inflammatory and hematological parameters were determined in serum or whole blood samples. The inflammatory status was higher in diabetic than in control rats, whereas the hematological parameters were lower in the diabetic rats than in the control rats. Hepcidin mRNA expression was significantly lower in the V-treated diabetic rats than in control and untreated diabetic rats. The inflammatory status remained at a similar level as the untreated diabetic group. However, the hematological profile improved after the V-treatment, reaching similar levels to those found in the control group. Serum iron level was higher in V-treated than in untreated diabetic rats. We conclude that V reduces gene expression of hepcidin in diabetic rats, improving the anemic state caused by diabetes.Consejeria de Innovacion, Ciencia y Empresa, Andalusian Regional Government P06-CTS-01435Spanish Ministry of Economy and Competitivity SAF2011-29648Instituto de Salud Carlos III European Commissio