Open Access
Nutritional interventions with bacillus coagulans improved glucose metabolism and hyperinsulinemia in mice with acute intermittent porphyria
(MDPI, 2023) Longo, Miriam; Jericó, Daniel; Córdoba, Karol M.; Riezu Boj, José I.; Urtasun Alonso, Raquel; Solares, Isabel; Sampedro, Ana; Collantes, María; Peñuelas, Iván; Moreno Aliaga, María J.; Ávila, Matías A.; Di Pierro, Elena; Barajas Vélez, Miguel Ángel; Milagro Yoldi, F. I.; Dongiovanni, Paola; Fontanellas, Antonio; Ciencias de la Salud; Osasun Zientziak
Acute intermittent porphyria (AIP) is a metabolic disorder caused by mutations in the porphobilinogen deaminase (PBGD) gene, encoding the third enzyme of the heme synthesis pathway. Although AIP is characterized by low clinical penetrance (~1% of PBGD mutation carriers), patients with clinically stable disease report chronic symptoms and frequently show insulin resistance. This study aimed to evaluate the beneficial impact of nutritional interventions on correct carbohydrate dysfunctions in a mouse model of AIP that reproduces insulin resistance and altered glucose metabolism. The addition of spores of Bacillus coagulans in drinking water for 12 weeks modified the gut microbiome composition in AIP mice, ameliorated glucose tolerance and hyperinsulinemia, and stimulated fat disposal in adipose tissue. Lipid breakdown may be mediated by muscles burning energy and heat dissipation by brown adipose tissue, resulting in a loss of fatty tissue and improved lean/fat tissue ratio. Probiotic supplementation also improved muscle glucose uptake, as measured using Positron Emission Tomography (PET) analysis. In conclusion, these data provide a proof of concept that probiotics, as a dietary intervention in AIP, induce relevant changes in intestinal bacteria composition and improve glucose uptake and muscular energy utilization. Probiotics may offer a safe, efficient, and cost-effective option to manage people with insulin resistance associated with AIP.
Open Access
Comparison of 0.12% chlorhexidine and a new bone bioactive liquid, BBL, in mouthwash for oral wound healing: a randomized, double blind clinical human trial
(MDPI, 2022) Ferrés‐Amat, Eduard; Al Madhoun, Ashraf; Ferrés-Amat, Elvira; Carrió, Neus; Barajas Vélez, Miguel Ángel; Al-Madhoun, Areej Said; Ferrés-Padró, Eduard; Marti, Carles; Atari, Maher; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa, OTRI project, reference number 2020907094
Following surgery, healing within the oral cavity occurs in a hostile environment, and proper oral care and hygiene are required to accelerate recovery. The aim of the current study is to investigate and compare the bioreactivity characteristics of mouthwashes based on either chlorhexidine (CHX) or a novel bone bioactive liquid (BBL) in terms of oral healing within seven days application post-surgery. A randomized, double blind clinical trial was conducted in 81 patients, wherein the mouthwashes were applied twice a day for a period of 7 days. The visual analog scale (VAS) protocol was applied to determine pain index scores. Early wound healing index (EHI) score was determined for evaluating oral cavity healing progress. No adverse effects were observed using the mouthwashes, but CHX application resulted in stained teeth. Applications of both CHX and BBL were sufficient to reduce pain over a period of 7 days. However, the BBL group demonstrated a statistically significant reduction in VAS scores starting on day 4. The EHI scores were significantly higher in the BBL group compared with the CHX group, independent of tooth location. No differences in either VAS or EHI scores due to gender were observed. Compared with the commercially available CHX mouthwash, application of the BBL mouthwash reduced pain and accelerated oral cavity healing to a greater extent, suggesting it effectively improves the oral cavity microenvironment at the wound site in mediating soft tissue regeneration.
Open Access
New insights into immunotherapy strategies for treating autoimmune diabetes
(MDPI, 2019) Cabello Olmo, Miriam; Araña Ciordia, Miriam; Radichev, Ilian; Smith, Paul; Huarte, Eduardo; Barajas Vélez, Miguel Ángel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Type 1 diabetes mellitus (T1D) is an autoimmune illness that affects millions of patients worldwide. The main characteristic of this disease is the destruction of pancreatic insulin-producing beta cells that occurs due to the aberrant activation of different immune effector cells. Currently, T1D is treated by lifelong administration of novel versions of insulin that have been developed recently; however, new approaches that could address the underlying mechanisms responsible for beta cell destruction have been extensively investigated. The strategies based on immunotherapies have recently been incorporated into a panel of existing treatments for T1D, in order to block T-cell responses against beta cell antigens that are very common during the onset and development of T1D. However, a complete preservation of beta cell mass as well as insulin independency is still elusive. As a result, there is no existing T1D targeted immunotherapy able to replace standard insulin administration. Presently, a number of novel therapy strategies are pursuing the goals of beta cell protection and normoglycemia. In the present review we explore the current state of immunotherapy in T1D by highlighting the most important studies in this field, and envision novel strategies that could be used to treat T1D in the future.
Open Access
Elovanoids counteract inflammatory signaling, autophagy, endoplasmic reticulum stress, and eenescence gene programming in human nasal epithelial cells exposed to allergens
(MDPI, 2022) Resano Lizaldre, Alfredo; Bhattacharjee, Surjyadipta; Barajas Vélez, Miguel Ángel; Do, Khanh V.; Aguado Jiménez, Roberto; Rodríguez, David; Palacios Peláez, Ricardo; Bazán, Nicolás G.; Ciencias de la Salud; Osasun Zientziak
To contribute to further understanding the cellular and molecular complexities of inflammatory-immune responses in allergic disorders, we have tested the pro-homeostatic elovanoids (ELV) in human nasal epithelial cells (HNEpC) in culture challenged by several allergens. ELV are novel bioactive lipid mediators synthesized from the omega-3 very-long-chain polyunsaturated fatty acids (VLC-PUFA,n-3). We ask if: (a) several critical signaling events that sustain the integrity of the human nasal epithelium and other organ barriers are perturbed by house dust mites (HDM) and other allergens, and (b) if ELV would participate in beneficially modulating these events. HDM is a prevalent indoor allergen that frequently causes allergic respiratory diseases, including allergic rhinitis and allergic asthma, in HDM-sensitized individuals. Our study used HNEpC as an in vitro model to study the effects of ELV in counteracting HDM sensitization resulting in inflammation, endoplasmic reticulum (ER) stress, autophagy, and senescence. HNEpC were challenged with the following allergy inducers: LPS, poly(I:C), or Dermatophagoides farinae plus Dermatophagoides pteronyssinus extract (HDM) (30 µg/mL), with either phosphate-buffered saline (PBS) (vehicle) or ELVN-34 (500 nM). Results show that ELVN-34 promotes cell viability and reduces cytotoxicity upon HDM sensitization of HNEpC. This lipid mediator remarkably reduces the abundance of pro-inflammatory cytokines and chemokines IL-1β, IL-8, VEGF, IL-6, CXCL1, CCL2, and cell adhesion molecule ICAM1 and restores the levels of the pleiotropic anti-inflammatory IL-10. ELVN-34 also lessens the expression of senescence gene programming as well as of gene transcription engaged in pro-inflammatory responses. Our data also uncovered that HDM triggered the expression of key genes that drive autophagy, unfolded protein response (UPR), and matrix metalloproteinases (MMP). ELVN-34 has been shown to counteract these effects effectively. Together, our data reveal a novel, pro-homeostatic, cell-protective lipid-signaling mechanism in HNEpC as potential therapeutic targets for allergies.
Open Access
Generation and characterization of human iPSC line generated from mesenchymal stem cells derived from adipose tissue
(Elsevier, 2016) Zapata Linares, Natalia; Rodríguez, Saray; Mazo, Manuel; Abizanda, Gloria; Barajas Vélez, Miguel Ángel; Ciencias de la Salud; Osasun Zientziak
In this work, mesenchymal stem cells derived from adipose tissue (ADSCs) were used for the generation of the human-induced pluripotent stem cell line G15.AO. Cell reprogramming was performed using retroviral vectors containing the Yamanaka factors, and the generated G15.AO hiPSC line showed normal karyotype, silencing of the exogenous reprogramming factors, induction of the typical pluripotency-associated markers, alkaline phosphatase enzymatic activity, and in vivo and in vitro differentiation ability to the three germ layers.
Open Access
Experimental pilot study after surgery on a food supplement for athletes to protect articular knee cartilage. A functional and biochemical study
(Federación Española de Medicina del Deporte, 2021) Alfaro Adrián, Jesús; Araña Ciordia, Miriam; Barajas Vélez, Miguel Ángel; Ciencias de la Salud; Osasun Zientziak
En este estudio experimental doble ciego se evalúa la eficacia de la suplementación condroprotectora (Carticure Plus®, 5000 mg Colágeno (Péptidos Bioactivos) altamente asimilable, 1500 mg Glucosamina clorhidrato, 1200 mg Condroitín sulfato, 1,1 mg Cobre, 80 mg Vitamina C, 2 mg Manganeso) en pacientes con patología ligamentosa y meniscal que han requerido cirugía artroscópica. Se seleccionaron 12 pacientes con lesión ligamentosa y 12 pacientes con meniscopatía a los que se les procedió a la medición de distintos marcadores inflamatorios mediante ELISA, colágeno 2A y ácido hialurónico, además de a la evalua¬ción del dolor así como la funcionalidad y calidad de vida a través de EVA (Escala Visual Analógica), WOMAC (Western Ontario McMaster Universities Osteoarthritis Index) y KOOS (Knee Injury and Osteoarthritis Outcome Score). Se observaron diferencias estadísticamente significativas de mejoría clínica a favor de Carticure Plus®, con una mejora de la capacidad funcional de la escala WOMAC del 76 % frente a un 53% del placebo para el conjunto de pacientes y con una clara mejoría en el primer mes en lesión meniscal, en mejora de las actividades de la vida diaria (KOOS), Carticure Plus® 31% frente a placebo -1%, actividad deportiva (Carticure Plus® 41% vs Placebo 13,2%), actividades deportivas y recreativas (Carticure Plus® 128% vs Placebo 10,4%). Por otro lado, en lesión ligamentosa se observa una mejoría en calidad de vida (KOOS) Carticure Plus® 75% vs Placebo -8,8% y dolor (KOOS) Carticure Plus® 49,6% vs Placebo 0,3% en el primer mes respecto al basal. En el conjunto de pacientes, el dolor (KOOS) Carticure Plus® 31,4% vs Placebo 1,3% y actividades de la vida diaria (KOOS) Carticure Plus® 43,9% vs Placebo 27,1% en el tercer mes respecto al basal se asocian a una mejora a Carticure Plus® en comparación al placebo. A pesar del pequeño tamaño muestral, es destacable el hecho de haber encontrado diferencias estadísticamente significativas que podría presu¬poner la eficacia de Carticure Plus®.
Open Access
Lactiplantibacillus plantarum DSM20174 attenuates the progression of non-alcoholic fatty liver disease by modulating gut microbiota, improving metabolic risk factors, and attenuating adipose inflammation
(MDPI, 2022) Riezu Boj, José I.; Barajas Vélez, Miguel Ángel; Pérez Sánchez, Tania; Pajares Villandiego, María Josefa; Araña Ciordia, Miriam; Milagro Yoldi, F. I.; Urtasun Alonso, Raquel; Ciencias de la Salud; Osasun Zientziak
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, reaching epidemic proportions worldwide. Targeting the gut–adipose tissue–liver axis by modulating the gut microbiota can be a promising therapeutic approach in NAFLD. Lactiplantibacillus plantarum, a potent lactic-acid-producing bacterium, has been shown to attenuate NAFLD. However, to our knowledge, the possible effect of the Lactiplantibacillus plantarum strain DSM20174 (L.p. DSM20174) on the gut–adipose tissue axis, diminishing inflammatory mediators as fuel for NAFLD progression, is still unknown. Using a NAFLD mouse model fed a high-fat, high-fructose (HFHF) diet for 10 weeks, we show that L.p DSM20174 supplementation of HFHF mice prevented weight gain, improved glucose and lipid homeostasis, and reduced white adipose inflammation and NAFLD progression. Furthermore, 16S rRNA gene sequencing of the faecal microbiota suggested that treatment of HFHF-fed mice with L.p DSM20174 changed the diversity and altered specific bacterial taxa at the levels of family, genus, and species in the gut microbiota. In conclusion, the beneficial effects of L.p DSM20174 in preventing fatty liver progression may be related to modulations in the composition and potential function of gut microbiota associated with lower metabolic risk factors and a reduced M1-like/M2-like ratio of macrophages and proinflammatory cytokine expression in white adipose tissue and liver.
Open Access
Histologic and histomorphometric evaluation of a new bioactive liquid bbl on implant surface: a preclinical study in foxhound dogs
(MDPI, 2021) Ferrés‐Amat, Eduard; Al Madhoun, Ashraf; Ferrés-Amat, Elvira; Al Demour, Saddam; Ababneh, Mera A.; Ferrés-Padró, Eduard; Marti, Carles; Carrió, Neus; Barajas Vélez, Miguel Ángel; Atari, Maher; Ciencias de la Salud; Osasun Zientziak
Background: bioactive chemical surface modifications improve the wettability and osse-ointegration properties of titanium implants in both animals and humans. The objective of this animal study was to investigate and compare the bioreactivity characteristics of titanium implants (BLT) pre‐treated with a novel bone bioactive liquid (BBL) and the commercially available BLT‐SLA active. Methods: forty BLT‐SLA titanium implants were placed in in four foxhound dogs. Animals were divided into two groups (n = 20): test (BLT‐SLA pre‐treated with BBL) and control (BLT‐SLA active) implants. The implants were inserted in the post extraction sockets. After 8 and 12 weeks, the animals were sacrificed, and mandibles were extracted, containing the implants and the surrounding soft and hard tissues. Bone‐to‐implant contact (BIC), inter‐thread bone area percentage (ITBA), soft tissue, and crestal bone loss were evaluated by histology and histomorphometry. Results: all animals were healthy with no implant loss or inflammation symptoms. All implants were clinically and histologically osseo‐integrated. Relative to control groups, test implants demon-strated a significant 1.5‐ and 1.7‐fold increase in BIC and ITBA values, respectively, at both assessment intervals. Crestal bone loss was also significantly reduced in the test group, as compared with controls, at week 8 in both the buccal crests (0.47 ± 0.32 vs 0.98 ± 0.51 mm, p < 0.05) and lingual crests (0.39* ± 0.3 vs. 0.89 ± 0.41 mm, p < 0.05). At week 12, a pronounced crestal bone loss improvement was observed in the test group (buccal, 0.41 ± 0.29 mm and lingual, 0.54 ± 0.23 mm). Tissue thickness showed comparable values at both the buccal and lingual regions and was significantly improved in the studied groups (0.82–0.92 mm vs. 33–48 mm in the control group). Conclusions: Relative to the commercially available BLT‐SLA active implants, BLT‐SLA pre‐treated with BBL showed improved histological and histomorphometric characteristics indicating a reduced titanium surface roughness and improved wettability, promoting healing and soft and hard tissue regeneration at the implant site.
Open Access
Randomized clinical trial: bone bioactive liquid improves implant stability and osseointegration
(MDPI, 2024-10-01) Al Madhoun, Ashraf; Meshal, Khaled; Carrió, Neus; Ferrés‐Amat, Eduard; Ferrés-Amat, Elvira; Barajas Vélez, Miguel Ángel; Jiménez-Escobar, Ana Leticia; Al-Madhoun, Areej Said; Saber, Alaa; Abou Alsamen, Yazan; Marti, Carles; Atari, Maher; Ciencias de la Salud; Osasun Zientziak; Institute for Multidisciplinary Research in Applied Biology - IMAB; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
Implant stability can be compromised by factors such as inadequate bone quality and infection, leading to potential implant failure. Ensuring implant stability and longevity is crucial for patient satisfaction and quality of life. In this multicenter, randomized, double-blind clinical trial, we assessed the impact of a bone bioactive liquid (BBL) on the Galaxy TS implant's performance, stability, and osseointegration. We evaluated the impact stability, osseointegration, and pain levels using initial stability quotient (ISQ) measurements, CBCT scans, and pain assessment post-surgery. Surface analysis was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In vitro studies examined the BBL's effects on dental pulp pluripotent stem cells' (DPPSCs') osteogenesis and inflammation modulation in human macrophages. All implants successfully osseointegrated, as demonstrated by the results of our clinical and histological studies. The BBL-treated implants showed significantly lower pain scores by day 7 (p < 0.00001) and improved stability by day 30 (ISQ > 62.00 ± 0.59, p < 8 × 10-7). By day 60, CBCT scans revealed an increased bone area ratio in BBL-treated implants. AFM images demonstrated the BBL's softening and wettability effect on implant surfaces. Furthermore, the BBL promoted DPPSCs' osteogenesis and modulated inflammatory markers in human primary macrophages. This study presents compelling clinical and biological evidence that BBL treatment improves Galaxy TS implant stability, reduces pain, and enhances bone formation, possibly through surface tension modulation and immunomodulatory effects. This advancement holds promise for enhancing patient outcomes and implant longevity.
Open Access
Antidiabetic effects of Pediococcus acidilactici pA1c on HFD-induced mice
(MDPI, 2022) Cabello Olmo, Miriam; Oneca Agurruza, María; Pajares Villandiego, María Josefa; Jiménez, Maddalen; Ayo, Josune; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, 0011-1365-2020-000086
Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.