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
Chemically defined conditions mediate an efficient induction of dental pulp pluripotent-like stem cells into hepatocyte-like cells
(Hindawi, 2021) Gil-Recio, Carlos; Montori, Sheyla; Al Demour, Saddam; Ababneh, Mera A.; Ferrés-Padró, Eduard; Marti, Carles; Ferrés-Amat, Elvira; Barajas Vélez, Miguel Ángel; Al Madhoun, Ashraf; Atari, Maher; Ciencias de la Salud; Osasun Zientziak
Liver diseases are major causes of morbidity and mortality. Dental pulp pluripotent-like stem cells (DPPSCs) are of a considerable promise in tissue engineering and regenerative medicine as a new source of tissue-specific cells; therefore, this study is aimed at demonstrating their ability to generate functional hepatocyte-like cells in vitro. Cells were differentiated on a collagen scaffold in serum-free media supplemented with growth factors and cytokines to recapitulate liver development. At day 5, the differentiated DPPSC cells expressed the endodermal markers FOXA1 and FOXA2. Then, the cells were derived into the hepatic lineage generating hepatocyte-like cells. In addition to the associated morphological changes, the cells expressed the hepatic genes HNF6 and AFP. The terminally differentiated hepatocyte-like cells expressed the liver functional proteins albumin and CYP3A4. In this study, we report an efficient serum-free protocol to differentiate DPPSCs into functional hepatocyte-like cells. Our approach promotes the use of DPPSCs as a new source of adult stem cells for prospective use in liver regenerative medicine.
Open Access
Influence of storage temperature and packaging on bacteria and yeast viability in a plant-based fermented food
(MDPI, 2020) Cabello Olmo, Miriam; Oneca Agurruza, María; Torre Hernández, Paloma; Díaz, Jesús Vicente; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Agronomía, Biotecnología y Alimentación; Agronomia, Bioteknologia eta Elikadura; Gobierno de Navarra / Nafarroako Gobernua
Optimization of food storage has become a central issue for food science and biotechnology, especially in the field of functional foods. The aim of this work was to investigate the influence of different storage strategies in a fermented food product (FFP) and further determine whether the regular storage (room temperature (RT) and standard packaging (SP)) could be refined. Eight experimental conditions (four different temperatures × two packaging) were simulated and changes in FFP’s microbial ecology (total bacteria, lactic acid bacteria (LAB), and yeasts) and physicochemical characteristics (pH and moisture content (MC)) were determined following 1, 3, 6, and 12 months. All conditions tested showed a decline in microbial content due to the effect of the temperature, 37 ◦C being the most detrimental condition, while −20 and 4 ◦C seemed to be better than RT in some parameters. Vacuum packaging (VP) only had a major effect on MC and we found that VP preserved greater MC values than SP at 3, 6, and 12 months. The correlation analysis revealed that total bacteria, LAB, and yeasts were positively associated, and also both pH and MC showed a correlation. According to our results and with the purpose to maintain the load of viable microorganisms, we observed that the best storage conditions should contemplate SP and freezing or cooling temperature during a period no longer than 3 months.
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
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
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
Development, analysis, and sensory evaluation of improved bread fortified with a plant-based fermented food product
(MDPI, 2023) Cabello Olmo, Miriam; Krishnan, Padmanaban G.; Araña Ciordia, Miriam; Oneca Agurruza, María; Díaz, Jesús Vicente; Barajas Vélez, Miguel Ángel; Rovai, Maristela; Ciencias de la Salud; Osasun Zientziak
In response to the demand for healthier foods in the current market, this study aimed to develop a new bread product using a fermented food product (FFP), a plant-based product composed of soya flour, alfalfa meal, barley sprouts, and viable microorganisms that showed beneficial effects in previous studies. White bread products prepared with three different substitution levels (5, 10, and 15%) of FFP were evaluated for physical characteristics (loaf peak height, length, width), color indices (lightness, redness/greenness, yellowness/blueness), quality properties (loaf mass, volume, specific volume), protein content, crumb digital image analysis, and sensory characteristics. The results revealed that FFP significantly affected all studied parameters, and in most cases, there was a dose–response effect. FFP supplementation affected the nutritional profile and increased the protein content (p < 0.001). The sensory test indicated that consumer acceptance of the studied sensory attributes differed significantly between groups, and bread with high levels of FFP (10 and 15% FFP) was generally more poorly rated than the control (0%) and 5% FFP for most of the variables studied. Despite this, all groups received acceptable scores (overall liking score ≥ 5) from consumers. The sensory analysis concluded that there is a possible niche in the market for these improved versions of bread products.
Open Access
A fermented food product containing lactic acid bacteria protects ZDF rats from the development of type 2 diabetes
(MDPI, 2019) Cabello Olmo, Miriam; Oneca Agurruza, María; Torre Hernández, Paloma; Sainz, Neira; Moreno Aliaga, María J.; Guruceaga, Elizabeth; Díaz, Jesús Vicente; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Ciencias; Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Type 2 diabetes (T2D) is a complex metabolic disease, which involves a maintained hyperglycemia due to the development of an insulin resistance process. Among multiple risk factors, host intestinal microbiota has received increasing attention in T2D etiology and progression. In the present study, we have explored the effect of long-term supplementation with a non-dairy fermented food product (FFP) in Zucker Diabetic and Fatty (ZDF) rats T2D model. The supplementation with FFP induced an improvement in glucose homeostasis according to the results obtained from fasting blood glucose levels, glucose tolerance test, and pancreatic function. Importantly, a significantly reduced intestinal glucose absorption was found in the FFP-treated rats. Supplemented animals also showed a greater survival suggesting a better health status as a result of the FFP intake. Some dissimilarities have been observed in the gut microbiota population between control and FFP-treated rats, and interestingly a tendency for better cardiometabolic markers values was appreciated in this group. However, no significant differences were observed in body weight, body composition, or food intake between groups. These findings suggest that FFP induced gut microbiota modifications in ZDF rats that improved glucose metabolism and protected from T2D development.
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
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.